Involvement of glucagon-like peptide 1 in the glucose homeostasis regulation in obese and pituitary-dependent hyperadrenocorticism affected dogs

The incretin glucagon-like peptide 1 (GLP-1) enhances insulin secretion. The aim of this study was to assess GLP-1, glucose and insulin concentrations, Homeostatic Model Assessment (HOMA_{insulin sensitivity} and HOMA_{β-cell function}) in dogs with pituitary-dependent hyperadrenocorticism (PDH), and compare these values with those in normal and obese dogs. The Oral Glucose Tolerance Test was performed and the glucose, GLP-1 and insulin concentrations were evaluated at baseline, and after 15, 30, 60 and 120 minutes. Both basal concentration and those corresponding to the subsequent times, for glucose, GLP-1 and insulin, were statistically elevated in PDH dogs compared to the other groups. Insulin followed a similar behaviour together with variations of GLP-1. HOMA_{insulin sensitivity} was statistically decreased and HOMA_{β-cell function} increased in dogs with PDH. The higher concentrations of GLP-1 in PDH could play an important role in the impairment of pancreatic β-cells thus predisposing to diabetes mellitus.     

Distinct adiponectin profiles might contribute to differences in susceptibility to type 2 diabetes in dogs and humans

Dogs develop obesity-associated insulin resistance but not type 2 diabetes mellitus. Low adiponectin is associated with progression to type 2 diabetes in obese humans. The aims of this study were to compare total and high molecular weight (HMW) adiponectin and the ratio of HMW to total adiponectin (S_A) between dogs and humans and to examine whether total or HMW adiponectin or both are associated with insulin resistance in naturally occurring obese dogs. We compared adiponectin profiles between 10 lean dogs and 10 lean humans and between 6 lean dogs and 6 age- and sex-matched, client-owned obese dogs. Total adiponectin was measured with assays validated in each species. We measured S_A with velocity centrifugation on sucrose gradients. The effect of total and HMW adiponectin concentrations on MINMOD-estimated insulin sensitivity was assessed with linear regression. Lean dogs had total and HMW adiponectin concentrations three to four times higher than lean humans (total: dogs 32 ± 5.6 mg/L, humans 10 ± 1.3 mg/L, P<0.001; HMW: dogs 25 ± 4.5 mg/L, humans 6 ± 1.3 mg/L, P<0.001) and a higher S_A (dogs: 0.78 ± 0.05; humans: 0.54 ± 0.08, P = 0.002). Adiponectin concentrations and S_A were not lower in obese dogs (0.76 ± 0.05 in both groups; P=1). Total adiponectin, HMW adiponectin, and S_A were not associated with insulin sensitivity in dogs. We propose that differences in adiponectin profiles between humans and dogs might contribute to the propensity of humans but not dogs to develop type 2 diabetes. Dogs with chronic, naturally occurring obesity do not have selectively reduced HMW adiponectin, and adiponectin does not appear to be important in the development of canine obesity-associated insulin resistance.     

Canine adiponectin: cDNA structure, mRNA expression in adipose tissues and reduced plasma levels in obesity

Adiponectin is a protein synthesized and secreted by adipocytes. Decreased adiponectin is responsible for insulin resistance and atherosclerosis associated with human obesity. We obtained a cDNA clone corresponding to canine adiponectin, whose nucleotide and deduced amino acid sequences were highly identical to those of other species. Adiponectin mRNA was detected in adipose tissues, but not in other tissues, of dogs. When 22 adult beagles were given a high-energy diet for 14 weeks, they became obese, showing heavier body weights, higher plasma leptin concentrations, but lower plasma adiponectin concentrations. The adiponectin concentrations of plasma samples collected from 71 dogs visiting veterinary practices were negatively correlated to plasma leptin concentrations, being lower in obese than non-obese dogs. These results are compatible with those reported in other species, and suggest that adiponectin is an index of adiposity and a target molecule for studies on diseases associated with obesity in dogs.     

Transition period-related changes in the abundance of the mRNAs of adiponectin and its receptors,of visfatin,and of fatty acid binding receptors in adipose tissue of high-yielding dairy cows

Adipose tissue expresses adipokines, which are involved in regulation of energy expenditure, lipid metabolism, and insulin sensitivity. To adapt for the transition from pregnancy to lactation, particularly in high-yielding dairy cows, adipokines, their receptors, and particular G-protein coupled receptors (GPRs) are of potential importance. Signaling by GPR 41 stimulates leptin release via activation by short-chain fatty acids; GPR 43/109A inhibits lipolysis, and GPR 109A thereby mediates the lipid-lowering effects of nicotinic acid and β–hydroxybutyrate. The aim of this study was to compare the mRNA expression of adiponectin and visfatin, adiponectin receptors 1 and 2 (AdipoR1/2), leptin receptor (obRb), insulin receptor as of the aforementioned GPRs during the transition period in high-yielding dairy cows. Biopsies from subcutaneous fat and blood samples were obtained from 10 dairy cows 1 week before and 3 weeks after calving. For AdipoR1 and AdipoR2 mRNA abundance as well as for leptin concentrations in plasma, a reduction (P ≤ .05) was observed postpartum; for visfatin and putative GPR 109A mRNA abundance in adipose tissue, there was a trend (P < .1) for analogous changes. In contrast, the mRNA content of obRb and GPR 41 in adipose tissue was higher (P ≤ .05) in samples from early lactation than in those from late gestation. Our results indicate decreasing adiponectin sensitivity in adipose tissue after calving, which might be involved in the reduced insulin sensitivity of adipose tissue during early lactation. In addition, visfatin, GPR 41, and GPR 109A may further modulate insulin sensitivity.     

Adiposity and adiponectin in dogs: investigation of causes of discrepant results between two studies

Although one study showed lower adiponectin concentrations in obese dogs, other recent studies indicate that adiponectin might not be decreased in obese dogs, raising the possibility that the physiology of adiponectin is different in dogs than in humans. The aim of this study was to investigate possible causes of the discrepancy between the two largest studies to date that assessed the association between adiposity and adiponectin concentration in dogs, including the validity of the assay, laboratory error, and the effects of breed, sex, and neuter status on the relationship between adiposity and adiponectin concentrations. Adiponectin concentrations measured with a previously validated adiponectin ELISA were compared with those estimated by Western blotting analysis of reduced and denatured plasma samples. The possibility of laboratory error and the effect of EDTA anticoagulant and aprotinin were tested. Adiponectin concentration was measured by ELISA in 20 lean dogs (10 male and 10 female, 5 neutered in each sex). There was close correlation between adiponectin concentrations measured by ELISA and those estimated by Western blotting analysis (r = 0.90; P < 0.001). There was no substantial effect of EDTA, aprotinin, or laboratory error on the results. There was confounding by neuter status of the relationship between adiposity and adiponectin concentrations, but adiponectin concentrations were not significantly lower in male than in female lean dogs (females, 36 mg/L; males, 26 mg/L; P > 0.20) and were not significantly lower in intact than in neutered lean male dogs (intact, 28 mg/L; neutered, 23 mg/L; P = 0.49). We conclude that the adiponectin ELISA previously validated for use in dogs appears to be suitable for determination of canine adiponectin concentrations and that testosterone does not appear to have a strong effect on plasma adiponectin concentrations in dogs. Obesity might decrease adiponectin concentrations in intact but not in neutered dogs.     

Assessment of Resting Insulin and Leptin Concentrations and Their Association With Managerial and Innate Factors in Horses

The purpose of this study was to determine how insulin and leptin concentrations varied in a large population of privately owned horses. Further, the study was designed to examine the relationships between insulin and leptin with innate (sex, age, breed) and managerial (diet, exercise) factors in these horses. Resting blood samples (for determination of glucose, insulin, and leptin concentrations), body condition scores, feed information, and health history were collected from 366 privately owned horses. In this group of horses, 48% were considered overweight (Body Condition Score ≥6) and 8% were considered hyperinsulinemic (insulin concentrations >30 μU/mL). Confirming the findings of studies within research herds, both insulin and leptin concentrations were found to be correlated with body condition score (P < .001). It was also found that geldings had higher insulin concentrations than mares (P < .05). Ponies were found to have higher insulin and leptin concentrations as well as higher body condition scores, than several other breeds examined. While not a specific measure of insulin sensitivity, resting insulin concentrations have been associated with quantitative measurements of insulin sensitivity and may be useful in large-scale studies for estimating insulin and glucose dynamics. Because of the association between insulin resistance and obesity with diseases such as laminitis, the findings of the present study may help owners identify horses that may be at risk for the development of such conditions.     

Effect of omega-3 polyunsaturated fatty acids and body condition on serum concentrations of adipokines in healthy dogs

Objective-To determine associations between serum concentrations of omega-3 polyunsaturated fatty acids or body condition and serum concentrations of adiponectin, leptin, insulin, glucose, or triglyceride in healthy dogs. Animals-62 healthy adult client-owned dogs. Procedures-Body condition score and percentage of body fat were determined. Blood samples were collected after food was withheld for 12 hours. Serum was harvested for total lipid determination, fatty acid analysis, and measurement of serum concentrations of adiponectin, leptin, insulin, glucose, and triglyceride. Associations between the outcome variables (adiponectin, leptin, insulin, glucose, and triglyceride concentrations) and each of several variables (age, sex, percentage of body fat, and concentrations of total lipid, α-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) were determined. Results-Serum concentrations of docosapentaenoic acid were significantly positively associated with concentrations of adiponectin and leptin and negatively associated with concentrations of triglyceride. Serum concentrations of α-linolenic acid were significantly positively associated with concentrations of triglyceride. No significant associations were detected between serum concentrations of eicosapentaenoic acid or docosahexaenoic acid and any of the outcome variables. Percentage of body fat was significantly positively associated with concentrations of leptin, insulin, and triglyceride but was not significantly associated with adiponectin concentration. Age was positively associated with concentrations of leptin, insulin, and triglyceride and negatively associated with concentrations of adiponectin. Sex did not significantly affect serum concentrations for any of the outcome variables. Conclusions and Clinical Relevance-Docosapentaenoic acid may increase serum concentrations of adiponectin and leptin and decrease serum triglyceride concentration in healthy dogs.     

Increased serum concentrations of adiponectin in canine hypothyroidism

Serum concentrations of adiponectin were compared between sex-matched hypothyroid (n = 18) and euthyroid (n = 18) client-owned dogs with comparable ages and body condition scores (BCS). Concentrations of adiponectin (mean; 95% confidence interval) were significantly (P < 0.01) higher in hypothyroid (17.2 µg/mL; 12.1–20.5 µg/mL) than healthy (8.0 µg/mL; 5.6–11.4 µg/mL) dogs following adjustment for potential confounders (BCS, age and sex). Serum concentrations of adiponectin were significantly negatively associated with concentrations of total thyroxine (P <0.05) and positively correlated with concentrations of cholesterol (r = 0.6, P <0.01) in hypothyroid dogs. In conclusion, this study demonstrated increased serum concentrations of adiponectin in dogs with hypothyroidism. Suggestive of the presence of resistance to adiponectin that could have contributed to development of hyperlipidemia and insulin resistance in these dogs or alternatively, could be a consequence of these metabolic alterations.     

Serum concentrations of leptin and adiponectin in dogs with chronic kidney disease

BackgroundAn imbalance in adipokines is associated with the progression of chronic kidney disease (CKD) in humans. However, alterations in adipokines in dogs with CKD remain unclear.ObjectivesTo examine whether adipokine concentrations in serum differ between healthy dogs and dogs with CKD and to determine the correlation between serum adipokine concentrations and CKD severity in dogs.AnimalsTwenty dogs with CKD and 10 healthy dogs.MethodsIn this cross‐sectional study, serum concentrations of leptin, adiponectin, interleukin (IL)‐6, IL‐10, IL‐18, and tumor necrosis factor (TNF)‐α were measured in healthy dogs and dogs with CKD, which were classified according to the International Renal Interest Society guidelines.ResultsSerum leptin concentrations were positively correlated with systolic arterial blood pressure (r = .41), creatinine concentrations (r = .39), and symmetric dimethylarginine concentrations (r = .73). Serum adiponectin concentrations (median [range]) in CKD dogs with borderline or non‐proteinuric (20.25 [14.9‐45.8] ng/mL) were significantly higher than those in proteinuric CKD dogs (13.95 [6.4‐22.1] ng/mL; P = .01). Serum IL‐6 (median [range]; 43.27 [24.30‐537.30] vs 25.63 [6.83‐61.03] pg/mL; P = .02), IL‐18 (median [range]; 25.98 [11.52‐280.55] vs 10.77 [3.53‐38.45] pg/mL; P = .01), and TNF‐α (median [range]) concentrations (11.44 [8.54‐38.45] vs 6.105 [3.97‐30.68] pg/mL; P = .02) were significantly different between proteinuric and borderline or non‐proteinuric CKD dogs.Conclusions and Clinical Importanceleptin and adiponectin concentrations in serum might be associated with severity of CKD and proteinuria in dogs with CKD, respectively.     

Investigation of the Effects of a Dietary Supplement on Insulin and Adipokine Concentrations in Equine Metabolic Syndrome/Insulin Dysregulation

High insulin concentrations are a common clinical feature of equine metabolic syndrome (EMS) and insulin dysregulation. Hyperinsulinemia can induce laminitis, so reduction of insulin concentrations in response to an oral challenge should decrease risk. In human studies, diets containing a polyphenol (resveratrol) led to improvements in insulin sensitivity. In rodents, the addition of leucine to a resveratrol supplement caused a decrease in the amount of resveratrol needed to achieve a clinical effect. We hypothesize a supplementation with a low dose of a synergistic polyphenol and amino acid blend including leucine (SPB+L) would improve metabolic health in EMS/insulin dysregulated horses. Fifteen EMS/ID horses received a high or low dose of SPB+ L daily for 6 weeks. Insulin during an oral sugar test (OST), body condition score, weight, baseline high-molecular-weight (HMW) adiponectin, triglycerides, nonesterified fatty acids, and tumor necrosis factor alpha were assessed before supplementation (PRE) and after supplementation (POST) via paired Student’s t-tests and a repeated-measures mixed-model analysis of variance (significant at P < .05). There were no differences between doses. Horses in the POST group weighed significantly less, had significantly higher baseline HMW adiponectin concentrations, and had significantly lower insulin concentrations at 60- and 75-minute time points (P < .05). Insulin concentrations of the horsesin the POST group, but not in the PRE group, were lower and similar to results from the study conducted three years before the present study (PRIOR) for 0- and 60-minute time points (P < .002). An increased HMW adiponectin level supports increasing insulin sensitivity after supplementation. These results suggest that SPB + L supplementation at either dose leads to improvements in the clinical manifestations of EMS/insulin dysregulation, potentially reducing laminitis risk.     

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.     

Fat mass,and not diet,has a large effect on postprandial leptin but not on adiponectin concentrations in cats

Leptin and adiponectin play important roles in carbohydrate and lipid metabolism in different species. Information is limited on the effects of diet, weight gain, and fat mass on their concentrations in cats. This study compared fasting and postprandial blood leptin and total adiponectin concentrations before and after 8 wk of ad libitum feeding to promote weight gain in adult cats (n = 32) fed either a low-carbohydrate, high-protein (23% and 47% ME) or a high-carbohydrate, low-protein (51% and 21% ME) diet. There were significant effects of total, abdominal, and nonabdominal fat mass, but not diet or body weight, on mean 24-h and peak leptin (P < 0.01); observed increases in mean and peak leptin were greatest for abdominal fat mass (50% and 56% increase for every extra 100 g, respectively). After weight gain, postprandial leptin concentration increased markedly relative to when cats were lean, and the duration of the increase was longer after a mean weight gain of 37% with the low-carbohydrate, high-protein diet group compared with 17% with the high-carbohydrate, low-protein group (P ≤ 0.01). Adiponectin was lower than fasting at some time points during the postprandial period in both groups (P ≤ 0.05). For both fasting and mean 24-h adiponectin, there was no significant diet effect (P ≥ 0.19) or changes in weight gain relative to when cats were lean (P ≥ 0.29). In conclusion, fat mass, and not diet, has a large effect on postprandial leptin but not adiponectin concentrations in cats.     

Markers for Predicting Overweight or Obesity of Broodmares

Obesity has become of great concern to all equine community from both veterinary and welfare points of view. For estimating obesity markers of brood mares, 17 mares with body conditions were subjected to blood sampling and ultrasound examination to measure rump fat for 6 consecutive weeks. Body length (L), girth (G), and height (H) were measured to estimate body weight (BW), body fat %, body fat mass (BFM) and body mass index (BMI). Mares were classified into three groups according to body condition score (BCS) and rump fat thickness (RF). Overweight mares (O) had BCS >7 and RF >7 mm, moderate (M) had BCS and RF >3 to ≤7, and emaciated (E) had BCS and RF ≤ 3 mm. Glucose, triglycerides, nitric oxide (NO), insulin, insulin-like growth factor-I (IGF-1), leptin, ovarian hormones, and thyroid hormones were measured. Results revealed that BCS, G, L, L × G × H, BW, RF, fat %, and BFM correlated significantly (P < .0001) with body condition. Tetraiodothyronine concentrations of E mares were significantly high (P = .04), but triiodothyronine concentrations tended (P = .07) to be low. Insulin (P = .06) and IGF-1 (P = .07) concentrations tended to be high in O mares. Moderate mares had the highest leptin concentrations (P = .007), but E mares had the lowest P4 concentrations (P = .01). Overweight mares had nonsignificantly high glucose, NO, and triglycerides. In conclusion, back fat and morphometric measurements are the easiest and simple assessment of overweight and obesity. Obese and overweight mares showed slight hyperinsulinemia, hypertriglyceridemia, and hyperglycemia. Hyperleptinemia alone is not indicative of obesity.     

Changes in plasma melanocyte-stimulating hormone,ACTH, prolactin,GH, LH,FSH, and thyroid-stimulating hormone in response to injection of sulpiride,thyrotropin-releasing hormone,or vehicle in insulin-sensitive and -insensitive mares

Six insulin-sensitive and 6 insulin-insensitive mares were used in a replicated 3 by 3 Latin square design to determine the pituitary hormonal responses (compared with vehicle) to sulpiride and thyrotropin-releasing hormone (TRH), 2 compounds commonly used to diagnose pituitary pars intermedia dysfunction (PPID) in horses. Mares were classified as insulin sensitive or insensitive by their previous glucose responses to direct injection of human recombinant insulin. Treatment days were February 25, 2012, and March 10 and 24, 2012. Treatments were sulpiride (racemic mixture, 0.01 mg/kg BW), TRH (0.002 mg/kg BW), and vehicle (saline, 0.01 mL/kg BW) administered intravenously. Blood samples were collected via jugular catheters at −10, 0, 5, 10, 20, 30, 45, 60, 90, and 120 min relative to treatment injection. Plasma ACTH concentrations were variable and were not affected by treatment or insulin sensitivity category. Plasma melanocyte-stimulating hormone (MSH) concentrations responded (P < 0.01) to both sulpiride and TRH injection and were greater (P < 0.05) in insulin-insensitive mares than in sensitive mares. Plasma prolactin concentrations responded (P < 0.01) to both sulpiride and TRH injection, and the response was greater (P < 0.05) for sulpiride; no effect of insulin sensitivity was observed. Plasma thyroid-stimulating hormone (TSH) concentrations responded (P < 0.01) to TRH injection only and were higher (P < 0.05) in insulin-sensitive mares in almost all time periods. Plasma LH and FSH concentrations varied with time (P < 0.05), particularly in the first week of the experiment, but were not affected by treatment or insulin sensitivity category. Plasma GH concentrations were affected (P < 0.05) only by day of treatment. The greater MSH responses to sulpiride and TRH in insulin-insensitive mares were similar to, but not as exaggerated as, those observed by others for PPID horses. In addition, the reduced TSH concentrations in insulin-insensitive mares are consistent with our previous observation of elevated plasma triiodothyronine concentrations in hyperleptinemic horses (later shown to be insulin insensitive as well).     

Serum Adipokine Concentrations in Dogs with Naturally Occurring Pituitary‐Dependent Hyperadrenocorticism

Background

An excess of intra‐abdominal fat is observed frequently in dogs with hyperadrenocorticism (HAC). Adipokine dysregulation is a possible cause of complications related to visceral obesity, but little information is available on adipokine in dogs with naturally occurring HAC.

Objectives

To examine the differences in the circulating adipokines concentrations in overweight dogs with and without pituitary‐dependent HAC (PDH).

Animals

Thirty healthy dogs and 15 client‐owned dogs with PDH.

Methods

Case–controlled observational study, which enrolled 15 overweight dogs diagnosed with PDH and 30 otherwise healthy dogs of similar body condition score. Nine of 15 dogs with PDH were treated with low‐dose trilostane twice daily and reassessed after treatment.

Results

The serum leptin (P < .0001) and insulin (P < .0001) concentrations were significantly higher in the PDH group (leptin, 22.8 ± 8.8 [mean ± SD]; insulin, 9.1 ± 6.1) than the healthy group (leptin, 4.9 ± 3.7; insulin, 1.9 ± 0.9). However, there were no significant differences in the adiponectin, resistin, tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6, IL‐10, and IL‐18 levels between the 2 groups. In the PDH group, the serum cortisol concentrations had a linear association with the leptin concentrations, and there were significant decreases in the leptin (P = .0039) and insulin (P = .0039) levels after trilostane treatment. However, the leptin and insulin levels remained higher after trilostane treatment than in healthy control dogs with similar body condition score.

Conclusions and Clinical Importance

Hypercortisolemia in dogs with PDH might upregulate the circulating leptin levels. However, a large population‐based study will be necessary to determine whether the upregulation of leptin is involved directly with the complications caused by HAC.     

Effects of leptin and adiponectin on the growth of porcine myoblasts are associated with changes in p44/42 MAPK signaling

We hypothesized that both adiponectin and leptin affect the growth of porcine skeletal muscle cells, with fatty acids acting as modifiers in adipokine action and that both adipokines influence the gene expression of their receptors. Therefore, the objective of this study was to investigate the effects of recombinant adiponectin and leptin on cell number (DNA) and DNA synthesis rate with and without oleic acid supplementation, on cell death, and on key intracellular signaling molecules of proliferating porcine myoblasts in vitro. Moreover, the mRNA expression of genes encoding for the leptin and adiponectin receptors (LEPR, ADIPOR1, ADIPOR2) as affected by leptin or adiponectin was examined. Recombinant porcine adiponectin (40 μg/mL) and leptin (20 ng/mL) increased DNA synthesis rate, measured as [³H]-thymidine incorporation (P < 0.01), reduced cell viability in terms of lactate dehydrogenase release (P < 0.05), or lowered DNA content after 24 h (P < 0.05). In adiponectin-treated cultures, oleic acid supplementation increased DNA synthesis rate and reduced cell number in a dose-dependent manner (P < 0.05). Both adiponectin (P = 0.07) and leptin (P < 0.05) induced a transient activation of p44/42 mitogen-activated protein kinase (MAPK) after 15 min, followed by decreases after 60 and 180 min (P < 0.05). Adiponectin tended to increase c-fos activation (P = 0.08) and decreased p53 activation at 180 min (P = 0.03). Both adiponectin and leptin down-regulated the abundance of ADIPOR2 mRNA and, transiently, of LEPR mRNA (P < 0.05). In conclusion, adiponectin and leptin may adversely affect the growth of porcine myoblasts, which is related to p44/42 MAPK signaling and associated with changes in ligand receptor gene expression.     

Factors Affecting the Glucose Response to Insulin Injection in Mares: Epinephrine, Short- and Long-Term Prior Feed Intake, Cinnamon Extract, and Omega-3 Fatty Acid Supplementation

Five experiments were conducted with mares to better define factors that might affect the assessment of insulin sensitivity via direct insulin injection, and to then apply this method of assessing insulin sensitivity to trials which tested two potential supplements for improving poor insulin sensitivity in horses. The experiments assessed the effects of the following: (1) previous administration of epinephrine, (2) overnight feed deprivation versus hay or pasture consumption, (3) 10-day acclimatization to hay in a dry lot versus pasture grazing, (4) cinnamon extract supplementation, and (5) fish oil supplementation on insulin sensitivity. Mares of known high and low insulin sensitivities were used in the first three experiments, whereas mares with low insulin sensitivities were used in the supplement trials. Epinephrine administration increased blood glucose concentrations (P < .05) and prevented the insulin-induced decrease in blood glucose concentrations in both sensitive and insensitive mares. Overnight feed deprivation decreased (P < .06) insulin sensitivity relative to overnight ad libitum access to hay, and both regimens resulted in reduced insulin sensitivity relative to overnight pasture availability; sensitive and insensitive mares responded similarly except when kept on pasture (P = .0854). Ten days of hay consumption in a dry lot reduced (P < .05) insulin sensitivity in insensitive mares, but not in sensitive mares, relative to pasture grazing. Supplementation with cinnamon extract or fish oil had no effect on insulin sensitivity of mares with known low insulin sensitivity under the conditions of these experiments.     

The GLP-1 mimetic exenatide potentiates insulin secretion in healthy cats

The glucagon-like peptide-1 mimetic exenatide has a glucose-dependent insulinotropic effect, and it is effective in controlling blood glucose (BG) with minimal side effects in people with type 2 diabetes. Exenatide also delays gastric emptying, increases satiety, and improves β-cell function. We studied the effect of exenatide on insulin secretion during euglycemia and hyperglycemia in cats. Nine young, healthy, neutered, purpose-bred cats were used in a randomized, cross-over design. BG concentrations during an oral glucose tolerance test were determined in these cats previously. Two isoglycemic glucose clamps (mimicking the BG concentration during the oral glucose tolerance test) were performed in each cat on separate days, one without prior treatment (IGC) and the second with exenatide (1 μg/kg) injected subcutaneously 2 h before (ExIGC). BG, insulin, and exenatide concentrations were measured, and glucose infusion rates were recorded and compared in paired tests between the two experiments. After exenatide injection, insulin serum concentrations increased significantly (2.4-fold; range 1.0- to 9.2-fold; P = 0.004) within 15 min. This was followed by a mild decrease in BG concentration and a return of insulin concentration to baseline despite a continuous increase in serum exenatide concentrations. Insulin area under the curve (AUC) during ExIGC was significantly higher than insulin AUC during IGC (AUC ratio, 2.0 ± 0.4; P = 0.03). Total glucose infused was not significantly different between IGC and ExIGC. Exenatide was detectable in plasma at 15 min after injection. The mean exenatide concentration peaked at 45 min and then returned to baseline by 75 min. Exenatide was still detectable in the serum of three of five cats 8 h after injection. No adverse reactions to exenatide were observed. In conclusion, exenatide affects insulin secretion in cats in a glucose-dependent manner, similar to its effect in other species. Although this effect was not accompanied by a greater ability to dispose of an intravenous glucose infusion, other potentially beneficial effects of exenatide on pancreatic β cells, mainly increasing their proliferation and survival, should be investigated in cats.