Growth hormone excess and the effect of octreotide in cats with diabetes mellitus

In this prospective study 16 cats with diabetes mellitus were examined for concurrent acromegaly by measuring plasma growth hormone (GH) and insulin-like growth factor-I concentrations, and magnetic resonance imaging (MRI) of the pituitary fossa. Additionally, the effects of octreotide administration on the plasma concentrations of glucose, GH, α-melanocyte-stimulating hormone (α-MSH), adrenocorticotrophic hormone (ACTH), and cortisol were measured.Five cats were diagnosed with hypersomatotropism. The pituitary was enlarged in these 5 cats and in 2 other cats. Six cats that required a maximum lente insulin dosage ≥1.5 IU/kg body weight per injection had pituitary enlargement and 5 of these cats had acromegaly. Plasma concentrations of GH, ACTH, and cortisol decreased significantly after single intravenous administration of the somatostatin analogue octreotide in the acromegalic cats. The effect on GH concentrations was more pronounced in some of the acromegalic cats than in others. In the non-acromegalic cats only ACTH concentrations decreased significantly. In both groups plasma glucose concentrations increased slightly but significantly, whereas α-MSH concentrations were not significantly affected.In conclusion, the incidence of hypersomatotropism with concomitant pituitary enlargement appears to be high among diabetic cats with severe insulin resistance. Some of these cats responded to octreotide administration with a pronounced decrease in the plasma GH concentration, which suggests that octreotide administration could be used as a pre-entry test for treatment with somatostatin analogues.     

Feline Acromegaly: An Underdiagnosed Endocrinopathy?

BACKGROUND: Feline acromegaly has been reported infrequently in the veterinary literature and current knowledge of this endocrinopathy is based on limited numbers of animals with relatively advanced clinical signs. HYPOTHESIS: This study was undertaken to screen diabetic cats for the presence of acromegaly. ANIMALS: Diabetic cats with variable control examined by general practitioners in the United Kingdom. METHODS: Blood samples were screened for the possible presence of acromegaly with basal serum concentrations of insulin-like growth factor 1 (IGF-1) and, when available, feline growth hormone (fGH). In patients with markedly increased IGF-1 concentrations intracranial computed tomography (CT) was offered, and in selected cats additional imaging was performed. RESULTS: IGF-1 was determined in 184 variably controlled diabetic cats; 59 cats had markedly increased IGF-1 concentrations (>1,000 ng/mL; reference interval, 208-443 ng/mL). Eighteen cats subsequently were examined, and acromegaly was confirmed in 17 cats. Notable findings included absence of a detectable pituitary mass lesion in some affected cats regardless of whether CT or magnetic resonance imaging (MRI) was used. Hypertension was not found to be a complication in the evaluated cats and respiratory stridor was more prevalent than previously reported. CONCLUSIONS AND CLINICAL IMPORTANCE: Measurement of IGF-1, growth hormone (GH), or both is useful in the diagnosis of acromegaly in cats.     

Evaluation of IGF-1 levels in cats with transient and permanent diabetes mellitus

It was investigated if IGF-1 levels in cats which experience diabetic remission (i.e. transient diabetes mellitus) differ from those in cats with permanent disease. Thirteen of 32 diabetic cats showed remission within 16 weeks after initiating insulin therapy, 19 cats continued to need insulin therapy. IGF-1 concentrations were measured before (t(0)), 1-3 (t(1)) and 4-8 (t(2)) weeks after initiating insulin therapy. No difference in IGF-1 levels was found between cats with transient and permanent diabetes at any point in time. In both groups of cats IGF-1 concentrations were significantly lower compared to those of controls before insulin administration. After starting insulin therapy IGF-1 increased significantly in both groups. In cats with transient diabetes IGF-1 levels were not different from controls already at t(1), whereas in cats with permanent diabetes it took until t(2). Although IGF-1 levels seem to normalize faster in cats with transient diabetes mellitus, measurement is not helpful to predict the course of the disease.     

Determination of the temporal relationship between porcine growth hormone, serum IGF-1 and cortisol concentrations in pigs

We found previously that porcine growth hormone (pGH) causes an increase in growth rate with a concurrent improvement in carcass composition in pigs. The somatomedin, insulin-like growth factor 1 (IGF-1), is though to play a major role in mediating some of the anabolic actions of GH, while the glucocorticoid hormones are potential counter-regulators of these effects. The present study was conducted to determine the temporal and dose-response relationship between GH administration and serum IGF-1 and cortisol concentrations in pigs. Twelve Yorkshire barrows, fitted with femoral artery catheters, were injected (im) with either 0, 10, 100 or 1,000 micrograms/kg pGH. Blood sampling began 40 min prior to pGH injection and was continued for 37 h. Serum GH, IGF-1 and cortisol concentrations were determined by radioimmunoassay. In control animals, serum GH concentrations ranged from 1.6 to 5.7 ng/ml over 37 h. In the animals treated with increasing doses of pGH, peak serum GH concentrations reached 28, 112 and 286 ng/ml and levels remained elevated for 4, 12 and 24 h, respectively. Serum IGF-1 concentrations were elevated by pGH after a lag time of 4 to 6 h. When the IGF-1 concentrations were integrated over time, the response appeared to be dose-dependent, with an ED50 of 710 micrograms/kg body weight (BW). Data for serum cortisol concentrations showed a great deal of individual variation. A transient increase in cortisol was observed, but only in the group treated with 1,000 micrograms pGH/kg BW. Cortisol levels returned to baseline 2 h after pGH injection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Circulating concentrations of insulin-like growth factor-1 in dogs with naturally occurring mitral regurgitation

Insulin-like growth factor-1 (IGF-1), which mediates most effects of growth hormone, has effects on cardiac mass and function, and plays an important role in the regulation of vascular tone. In humans, an inverse relationship between degree of heart failure (HF) and circulating IGF-1 concentrations has been found in several studies. In dogs with HF, few studies have focused on IGF-1. We examined circulating IGF-1 concentrations in dogs with mitral regurgitation (MR) caused by myxomatous mitral valve disease. Study 1 included 88 Cavalier King Charles Spaniels (CKCSs) with a broad range of asymptomatic MR (median serum IGF-1: 76.7 microg/L; 25-75 percentile, 59.8-104.9 microg/L). As expected, standard body weight and percentage under- or overweight correlated directly with IGF-1. MR (assessed in 4 different ways) did not correlate with IGF-1. In study 2, 28 dogs with severe MR and stable, treated congestive HF had similar serum IGF-1 concentrations (median, 100.8 g/L; 25-75 percentile, 74.9-156.5 microg/L) as 11 control dogs (79.6 microg/L; 25-75 percentile, 64.1-187.4 microg/L; P = .84). In study 3, the plasma IGF-1 concentration of 15 untreated CKCSs with severe MR was 16.4 +/- 24.2 microg/L lower (P = .02) at the examination when decompensated HF had developed (80.8 +/- 30.9 microg/L) than at a visit 1-12 months earlier (97.2 +/- 39.8 microg/L), possibly in part due to an altered state of nutrition. The studies document that circulating IGF-1 concentrations are not altered before development of congestive HF in dogs with naturally occurring MR, but decrease by approximately 20% with the development of untreated HE In treated HF, circulating IGF-1 concentrations apparently return to within the reference range.     

Serum Fructosamine Concentration as an Index of Glycemia in Cats With Diabetes Mellitus and Stress Hyperglycemia

The purpose of this study was to evaluate fructosamine concentrations in clinically healthy cats, sick cats with stress hyperglycemia, and untreated diabetic cats to determine the usefulness of this test in diagnosing diabetes mellitus in cats, and in differentiating the disease from stress-induced hyperglycemia. In addition, we evaluated if the degree of glycemic control in cats treated for diabetes influenced their serum fructosamine concentrations. In the 14 sick cats with stress hyperglycemia, the median serum fructosamine concentration (269 μmol/L) was not significantly different from the median value in the 26 clinically normal cats (252 μmol/L). Two of the 14 cats with stress hyperglycemia (14.3%) had serum fructosamine concentrations above the upper limit of the reference range (175 to 400 μmol/U; on the basis of these results, the test specificity was calculated as 0.86. In 30 cats with untreated diabetes mellitus, the median serum fructosamine concentration was 624 μmol/L, markedly higher than the value in either the normal cats or the cats with stress hyperglycemia. All but 2 of the 30 untreated diabetic cats (6.7%) had serum fructosamine concentration above the upper limit of the reference range; on the basis of these results, the sensitivity of serum fructosamine concentration as a diagnostic test for diabetes mellitus was 0.93. When 30 diabetic cats receiving treatment were divided into 3 groups according to their response to treatment (ie, poor, fair, and good), the 16 cats that had a good response to treatment had significantly lower serum concentrations of both glucose and fructosamine compared with cats that had either a fair or poor response to treatment. A significant correlation (r_s= .70, n = 100, P < .001) was found between serum concentrations of glucose and fructosamine. Results of this study indicate that quantification of serum fructosamine concentration is a meaningful test for the diagnosis of diabetes, for differentiating diabetes from stress hyperglycemia; and for monitoring the metabolic control in treated diabetic cats.     

Phenotypic expression of equine articular chondrocytes grown in three-dimensional cultures supplemented with supraphysiologic concentrations of insulin-like growth factor-1

OBJECTIVE: To assess the effects of supraphysiologic concentrations of insulin-like growth factor-1 (IGF-1) on morphologic and phenotypic responses of chondrocytes. SAMPLE POPULATION: Articular cartilage obtained from 2 young horses. PROCEDURE: Chondrocytes were suspended in fibrin cultures and supplemented with 25, 12.5, or 0 mg of IGF-1/ml of fibrin. Chondrocyte morphology and phenotypic expression were assessed histologically, using H&E and Alcian blue stains, immunoreaction to collagen type I and II, and in situ hybridization. Proteoglycan content, synthesis, and monomer size were analyzed. The DNA content was determined by bisbenzimide-fluorometric assay, and elution of IGF-1 into medium was determined by IGF-1 radioimmunoassay. RESULTS: Both 12.5 and 25 kg of IGF-1/ml enhanced phenotypic expression of chondrocytes without inducing detrimental cellular or metabolic effects. Highest concentration of IGF-1 (25 microg/ml) significantly increased total DNA content, glycosaminoglycan (GAG) content, GAG synthesis, and size of proteoglycan monomers produced, compared with cultures supplemented with 12.5 microg of IGF-1/ml or untreated cultures. Histologic examination confirmed these biochemical effects. Matrix metachromasia, type-II collagen in situ hybridization and immunoreaction were increased in cultures treated with 25 microg of IGF-1/ml, compared with cultures supplemented with 12.5 microg of IGF-1/ml or untreated cultures. CONCLUSIONS AND CLINICAL RELEVANCE: Chondrocytes exposed to high concentrations of IGF-1 maintained differentiated chondrocyte morphology and had enhanced synthesis of matrix molecules without inducing apparent detrimental effects on chondrocyte metabolism. These results suggest that application of such composites for in vivo use during cartilage grafting procedures should provide an anabolic effect on the grafted cells.     

Comparison of serum fructosamine and blood glycosylated hemoglobin concentrations for assessment of glycemic control in cats with diabetes mellitus.

OBJECTIVE: To correlate serum fructosamine concentrations with established measures of glycemic control and to compare serum fructosamine and blood glycosylated hemoglobin (GHb) concentrations as a means for assessing glycemic control in diabetic cats. DESIGN: Longitudinal cohort study. ANIMALS: 26 healthy cats, 5 cats with stress-induced hyperglycemia, 15 untreated diabetic cats, and 36 treated diabetic cats. PROCEDURE: Control of glycemia was classified and monitored and serum fructosamine and blood GHb concentrations were measured for 12 poorly controlled diabetic cats before and after improving glycemic control, 8 well-controlled treated diabetic cats before and after glycemic control deteriorated, and 5 cats with diabetes mellitus before and after onset of stress-induced hyperglycemia. RESULTS: Mean serum fructosamine and blood GHb concentrations were significantly higher in untreated diabetic cats, compared with healthy cats, and in 24 poorly controlled diabetic cats, compared with 12 well-controlled diabetic cats. Mean serum fructosamine and blood GHb concentrations decreased significantly in 12 poorly controlled diabetic cats after improving glycemic control and increased significantly in 8 well-controlled diabetic cats after glycemic control deteriorated. A significant stress-induced increase in mean blood glucose concentration was evident 12 hours after insulin administration, but not in 5 docile diabetic cats that became fractious. CLINICAL IMPLICATIONS: Serum fructosamine and blood GHb concentrations are clinically useful tools for monitoring control of glycemia in cats with diabetes mellitus.     

Remission of diabetes mellitus in cats cannot be predicted by the arginine stimulation test

Background: Cats with diabetes mellitus frequently achieve clinical remission, suggesting residual β‐cell function. Responsiveness of β‐cells to arginine persists the longest during diabetes progression, making the intravenous arginine stimulation test (IVAST) a useful tool to assess residual insulin and glucagon secretion. Hypothesis: Diabetic cats with and without remission will have different arginine‐induced insulin or glucagon response. Animals: Seventeen cats with diabetes, 7 healthy cats. Methods: Blood samples collected on admission and during subsequent IVAST. Glucose, insulin, and glucagon were measured. Response to IVAST was assessed by calculating the insulin and glucagon area under the curve (AUC) and the AUC glucagon‐to‐insulin ratio. Diabetic cats were treated with insulin and were followed for 18 weeks. Remission was defined as normoglycemia and disappearance of clinical signs of diabetes for ≥4 weeks, without requiring insulin. Results: Seven diabetic cats (41%) achieved remission. On admission, blood glucose concentration was significantly lower in cats with remission (median, 389 mg/dL; range, 342–536 mg/dL) than in those without remission (median, 506 mg/dL; range, 266–738 mg/dL). After IVAST, diabetic cats with remission had higher AUC glucagon‐to‐insulin ratios (median, 61; range, 34–852) than did cats without remission (median, 26; range, 20–498); glucose, insulin, and glucagon AUCs were not different. Diabetic cats had lower insulin AUC than did healthy cats but comparable glucagon AUC. Conclusions and Clinical Importance: Diabetic cats with and without remission have similar arginine‐stimulated insulin secretion on admission. Although cats with remission had lower blood glucose concentrations and higher AUC glucagon‐to‐insulin ratios, large overlap between groups prevents use of these parameters in clinical practice.     

The relationship between insulin-like growth factor-1, growth hormone, thyroid hormones and insulin in chickens selected for growth

The concentrations of circulating insulin-like growth factor I, growth hormone, insulin and thyroid hormones were measured in broilers selected for an increase in growth, broilers in which selection pressure was relaxed and in White Leghorns. Growth hormone levels increased in all lines between 3 and 4 weeks of age followed by a decline to adult levels. The lines with the slowest rate of growth had the highest growth hormone concentrations. Insulin-like growth factor I concentrations increased significantly in all three lines of birds during the 10 weeks of study and was significantly correlated with the increase in body weight. There were no consistent differences in plasma IGF-1 levels between the lines. Thyroxine levels increased consistently throughout the study but the levels of triiodothyronine decreased between 5 and 6 weeks of age in all lines. There were no consistent changes in plasma insulin levels. The highest rate of growth in these animals is accompanied by an increase in growth hormone concentration followed by an increase in plasma IGF-1. However, despite differences in plasma growth hormone, plasma concentrations of IGF-1 are not different between lines and are not related to between line differences in growth rate.     

Remission of Diabetes Mellitus in Cats with Diabetic Ketoacidosis

Background: Diabetic ketoacidosis (DKA) has long been considered a key clinical feature of type‐1 diabetes mellitus (DM) in humans although. An increasing number of cases of ketoacidosis have been reported in people with type‐2 DM. Hypothesis/Objectives: Cats initially diagnosed with DKA can achieve remission from diabetes. Cats with DKA and diabetic remission are more likely to have been administered glucocorticoids before diagnosis. Animals: Twelve cats with DKA and 7 cats with uncomplicated DM. Methods: Retrospective case review. Medical records of cats presenting with DKA or DM were evaluated. Diabetic remission was defined as being clinically unremarkable for at least 1 month after insulin withdrawal. The cats were assigned to 1 of 3 groups: (1) cats with DKA and diabetic remission; (2) cats with DKA without diabetic remission; and (3) cats with DM and diabetic remission. Results: Seven cats with DKA had remission from diabetes. These cats had significantly higher concentrations of leukocytes and segmented neutrophils, and significantly lower concentrations of eosinophils in blood and had pancreatic disease more often than did cats with uncomplicated DM and diabetic remission. With regard to pretreatment, 3/7 cats in group 1, 1/5 cats in group 2, and 1/7 cats in group 3 had been treated with glucocorticoids. Conclusions and Clinical Importance: Remission of DM in cats presenting with DKA is possible. Cats with DKA and remission have more components of a stress leucogram, pancreatic disease, and seemed to be treated more often with glucocorticoids than cats with uncomplicated DM and diabetic remission.     

Clinical usefulness of fructosamine measurements in diagnosing and monitoring feline diabetes mellitus

Fructosamines are glycated serum proteins that reflect long-term serum glucose concentrations in humans and several animal species. In the present study, blood samples were drawn from three populations of diabetic cats: untreated diabetic cats with clinical symptoms prevailing only a few days (n = 1), untreated diabetic cats with symptoms lasting more than two weeks (n = 6) and clinically well stabilised diabetic cats receiving insulin twice daily which showed no signs of disease (n = 4). All untreated diabetic cats showed elevated fructosamine measurements. Based on fructosamine measurements, clinically well stabilised diabetic cats could be subdivided further according to the degree of glycaemic control. Diabetic cats with satisfactory glycaemic control revealed fructosamine concentrations within or close to the reference range (146 to 271 umol/litre), whereas fructosamine concentrations above 400 umol/litre indicated insufficient glycaemic control. This study suggests that the fructosamine assay reflects persistently elevated serum glucose concentrations in cats and is a useful parameter for diagnosing and monitoring diabetes mellitus in cats.     

Pharmacology of a 40 IU/ml porcine lente insulin preparation in diabetic cats: findings during the first week and after 5 or 9 weeks of therapy.

The aim of this study was to measure the pharmacokinetics and pharmacodynamics of subcutaneously injected 40 IU/ml porcine lente insulin preparation (Caninsulin, Intervet BV, The Netherlands) in diabetic cats. The pharmacological properties of the insulin in poorly controlled or untreated cats were compared with those after several weeks of treatment, to determine if improved diabetic stability altered the pharmacology of this insulin. In addition, the pharmacological properties of intravenously injected 100 IU/ml regular porcine insulin (Actrapid MC, NovoNordisk, Denmark) were measured. Serial plasma samples were collected after subcutaneous injection of porcine lente insulin from 25 diabetic cats in the first week of admission to a 12-month diabetic treatment trial. Samples were also collected after 4 or 8 weeks of treatment, in those cats which had not achieved diabetic remission by this time. At this time, serial plasma samples were also collected from these cats after intravenous injection of porcine regular insulin. Plasma samples were assayed for glucose, anti-insulin antibodies were extracted using a PEG technique, and samples were assayed for insulin using an RIA kit with low sensitivity for endogenous feline insulin, but high sensitivity for exogenous porcine insulin in feline plasma. Caninsulin injected subcutaneously in diabetic cats led to a peak insulin concentration in plasma after 1.7+/-0.1 h, and a nadir of blood glucose after 4.1+/-0.3 h. Insulin and glucose concentrations returned to baseline within 12 h. There was no significant change in the onset or duration of Caninsulin action between the first week of treatment and 5 or 9 weeks of treatment. Actrapid MC injected intravenously had a peak insulin at 0.36+/-0.03 h, and a nadir of blood glucose at 1.9+/-0.3 h. Insulin and glucose returned to baseline within 6 h. It was concluded that Caninsulin injected subcutaneously has suitable pharmacological properties for the twice-daily treatment of diabetes mellitus in cats. In addition, Actrapid MC insulin injected intravenously has suitable pharmacological properties for injection every 4-6 h in diabetic cats.     

Insulin sensitivity in normal and diabetic cats

Estimates of in vivo insulin sensitivity (S(I)) can be derived from minimal model analysis of a frequently sampled intravenous glucose tolerance test (FSIVGTT). Modification of the FSIVGTT by the injection of insulin allows insulin sensitivity to be measured in diabetics. To establish and compare reference values for insulin sensitivity in clinically normal and diabetic cats, we subjected 10 clinically normal cats and five diabetic cats to the insulin-modified FSIVGTT with minimal model analysis. Diabetic cats had a significantly lower insulin sensitivity than clinically normal cats (P<0.05). Mean insulin sensitivity in clinically normal cats was 3.22x10(-4)/min/microU/ml (range 1.71-5.23x10(-4)/min/microU/ml). In contrast, the mean insulin sensitivity in diabetic cats was 0.58x10(-4)/min/microU/ml (range 0.136-0.88x10(-4)/min/microU/ml), or approximately six times less insulin sensitive than clinically normal cats. Mean glucose effectiveness in clinically normal cats was 0.030/min (range 0.021-0.045/min). Mean glucose effectiveness in diabetic cats was 0.014/min (range 0.008-0.021/min). Our data demonstrate that insulin resistance is a feature of feline diabetes mellitus and that diabetic cats have a similar relative decrease in insulin sensitivity to humans with type 2 diabetes.     

Diagnosis and management of diabetes mellitus in five cats with somatotrophic abnormalities

The clinical findings and management of five cats with abnormalities consistent with acromegaly were examined retrospectively. Growth hormone (GH) concentrations were elevated in four cats. In one, a minimal elevation of GH was accompanied by a marked elevation in insulin-like growth factor-1 (IGF-1). Insulin-like growth factor-1 concentrations supported the diagnosis in three of four cats measured, but was not elevated initially in one cat, despite a markedly elevated GH concentration. These findings suggest that elevated IGF-1 concentrations are a reliable indicator of acromegaly, but that values within the reference range do not exclude such a diagnosis. Clinical signs of acromegaly were similar to those previously reported, although upper respiratory stridor occurred in one cat, and insulin-resistant diabetes mellitus was not a consistent feature. Despite the lack of a widely available definitive treatment for acromegaly, good control of the clinical signs of diabetes mellitus can be achieved for long periods despite high doses of insulin often being required.     

Nutritionally induced relationships between insulin levels during the weaning-to-ovulation interval and reproductive characteristics in multiparous sows: I. Luteinizing hormone, follicle development, oestrus and ovulation

To get more insight in how insulin secretion patterns and corresponding insulin-like growth factor-1 (IGF-1) levels are related to luteinizing hormone (LH) secretion, follicle development and ovulation, 32 multiparous sows were fed either a dextrose plus lactose-containing diet at 4 h intervals (DL; each 150 g/day) or an isocaloric control diet at 12 h intervals (CTRL; containing soybean oil) during the weaning-to-ovulation interval (WOI). Insulin parameters (basal, peak levels and mean insulin) and IGF-1 levels during the WOI were similar for both treatments, but the insulin secretion pattern differed (related with feeding frequency and meal sizes). Oestrus and ovulation characteristics were not influenced by treatment. The LH surge was higher in CTRL compared with DL sows (3.73 vs 3.00 ng/ml; p = 0.03). Average diameter (6.5 vs 6.1 mm; p = 0.08) and uniformity (CV: 11 vs 15%, p = 0.02) of follicles ≥3 mm at day 4 after weaning was higher in CTRL compared with DL sows. Basal insulin levels were positively related with follicle diameter at ovulation (β = 0.05 mm/(μU/ml); p = 0.04) and negatively related with LH surge level (β = -0.07 (ng/ml)/(μU/ml); p = 0.01). Insulin area under the curve (AUC) (β = 0.037 (ng/ml)/1000 μU; p = 0.02) and IGF-1 levels (β = 0.002 (ng/ml)/(ng/ml); p < 0.01) were positively related to basal LH level around the LH surge. From these data, we conclude that insulin and IGF-1 levels during the WOI are related to LH secretion and follicle development. Not only the absolute level of insulin seems important, but also the pattern within a day in which insulin is secreted seems to affect LH secretion and development of pre-ovulatory follicles.     

Basal and Glucagon-Stimulated Plasma C-PeDtide Concentrations in Healthy Dogs, Dogs With Diabetes Millitus, and Dogs With Hyperadrenocorticism

Serum glucose and plasma C-peptide response to IV glucagon administration was evaluated in 24 healthy dogs, 12 dogs with untreated diabetes mellitus, 30 dogs with insulin-treated diabetes mellitus, and 8 dogs with naturally acquired hyperadrenocorticism. Serum insulin response also was evaluated in all dogs, except 20 insulin-treated diabetic dogs. Blood samples for serum glucose, serum insulin, and plasma C-peptide determinations were collected immediately before and 5,10,20,30, and (for healthy dogs) 60 minutes after IV administration of 1 mg glucagon per dog. In healthy dogs, the patterns of glucagon-stimulated changes in plasma C-peptide and serum insulin concentrations were identical, with single peaks in plasma C-peptide and serum insulin concentrations observed approximately 15 minutes after IV glucagon administration. Mean plasma C-peptide and serum insulin concentrations in untreated diabetic dogs, and mean plasma C-peptide concentration in insulin-treated diabetic dogs did not increase significantly after IV glucagon administration. The validity of serum insulin concentration results was questionable in 10 insulin-treated diabetic dogs, possibly because of anti-insulin antibody interference with the insulin radioimmunoassay. Plasma C-peptide and serum insulin concentrations were significantly increased (P < .001) at all blood sarnplkg times after glucagon administration in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Five-minute C-peptide increment, C-peptide peak response, total C-peptide secretion, and, for untreated diabetic dogs, insulin peak response and total insulin secretion were significantly lower (P < .001) in diabetic dogs, compared with healthy dogs, whereas these same parameters were significantly increased (P < .011 in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Although not statistically significant, there was a trend for higher plasma C-peptide concentrations in untreated diabetic dogs compared with insulin-treated diabetic dogs during the glucagon stimulation test. Baseline C-peptide concentrations also were significantly higher (P < .05) in diabetic dogs treated with insulin for less than 6 months, compared with diabetic dogs treated for longer than 1 year. Finally, 7 of 42 diabetic dogs had baseline plasma C-peptide concentrations greater than 2 SD (ie, >0.29 pmol/mL) above the normal mean plasma C-peptide concentration; values that were significantly higher, compared with results in healthy dogs (P < .001) and with the other 35 diabetic dogs (P < .001). In summary, measurement of plasma C-peptide concentration during glucagon stimulation testing allowed differentiation among healthy dogs, dogs with impaired β-cell function (ie, diabetes mellitusl, and dogs with increased β-cell responsiveness to glucagon (ie, insulin resistance). Plasma C-peptide concentrations during glucagon stimulation testing were variable in diabetic dogs and may represent dogs with type-1 and type-2 diabetes or, more likely, differences in severity of β-cell loss in dogs with type-1 diabetes. J Vet Intern Med 1996;10:116–122. Copyright © 1996 by the American College of Veterinary Internal Medicine.     

Effects of Body Condition and Protein Supplementation on LH Secretion and Luteal Function in Sheep

In ruminants, nutrition is one of the exogenous inputs affecting reproductive function at different levels of the hypothalamic-hypophyseal-gonadal axis. However, the exact mechanisms or even the identification of the signalling metabolic compounds by which nutrition affects reproductive function still need further clarification. The role of static body condition (BC) and its interaction with a short-term protein supplementation (PL), on secretion of metabolic hormones [growth hormone (GH), insulin and insulin-like growth factor-1 (IGF-1)], as well as on secretion of LH and progesterone (P4) was evaluated in sheep. Twenty-four Rambouillet ewes divided into two groups, with lower (LBC) and higher body condition (HBC), were randomly assigned within BC to one of two PL levels: low (LPL, 24% of crude protein; 14 g/animal/day), and high (HPL, 44% of crude protein; 30 g/animal/day). The secretion of GH, insulin, IGF-1 and LH was evaluated on day 10 of the oestrous cycle; appearance and timing of oestrous behaviour were previously detected using rams. Progesterone secretion was evaluated on day 13 of the same cycle. No differences were found (p > 0.05) between PL groups on serum GH concentrations during the sampling period (overall mean of 4.0 +/- 0.3 ng/ml), but a trend for lower values in HBC sheep was found (3.6 +/- 0.4 vs 4.4 +/- 0.4 ng/ml, p = 0.06). A BC effect was observed (p < 0.05) on serum IGF-1 level, with higher values in HBC sheep (p < 0.05). Neither BC nor PL affected (p > 0.05) secretion of LH and the number of corpora lutea, nor serum P4 and insulin concentrations. Results indicate a predominance of the static component of nutrition on sheep metabolic hormone responses, GH and IGF-1, with no effect of short-term PL on secretion of pituitary and ovarian hormones as well as luteal number and activity.     

Investigation of serum IGF-I levels amongst diabetic and non-diabetic cats

Since insulin-like growth factor-I (IGF-I) was first discovered as a mediator of glucose homeostasis, it has been extensively investigated in diabetes research in humans, rodents and primates. To date, however, relatively little work has been carried out on this hormone in the cat, despite the pathophysiological similarities between human and feline diabetes mellitus, as well as the relatively common nature of the disease in cats. This study reports on the IGF-I concentrations of 42 insulin treated diabetic cats and 25 normal cats. Diabetic subjects were grouped according to length of insulin treatment as either short, medium or long term. Analysis of variance (ANOVA) and Fischer's pair-wise comparisons revealed that mean IGF-I levels in short-term diabetic cats were significantly lower than those in normal cats whilst mean levels in long-term diabetics were significantly higher. The direction and extent of these alterations may have implications for our understanding of the pathophysiology of feline diabetes mellitus and for the use of this hormone in the diagnosis of acromegaly in diabetic cats.     

Beta cell and insulin antibodies in treated and untreated diabetic cats

Beta cell and insulin antibodies are involved in the pathogenesis of diabetes in human patients. Beta cell antibodies have also been found in about 50% of newly diagnosed diabetic dogs. This study's objective was to examine these antibodies' role in feline diabetes. The serum of 26 newly diagnosed untreated diabetic cats, 29 cats on insulin therapy, 30 cats with diseases other than diabetes, and 30 healthy cats was examined for beta cell and insulin antibodies. For beta cell antibody testing, purified beta cells from a radiation-induced transplantable rat insulinoma were used. Serum from cats in which anti-beta cell antibodies were induced by injecting a purified beta cell suspension subcutaneously was used as a positive control. Following incubation with test sera, fluorescein-labeled anti-cat immunoglobulins were used to visualize binding between the beta cells and cat gamma globulins. Each serum was tested on two different tumor preparations. For the detection of insulin antibodies, a charcoal separation method was used. It was found that none of the healthy cats, none of the newly diagnosed, untreated diabetic cats and none of the cats with diseases other than diabetes had antibodies against beta cells or against endogenous insulin. Four diabetic cats (14%) that had been treated with different insulin preparations had insulin antibodies.It is concluded that immune-mediated processes are not causing diabetes in the cat. Further studies are needed to evaluate if antibodies directed against exogenous insulin alter the response of diabetic cats to insulin.