Low-dietary protein intake induces problems with glucose homeostasis and results in hepatic steatosis in heavy milk-fed calves

We studied effects of protein intake at two protein-free energy intake levels on plasma glucose and insulin concentrations, urinary glucose excretion and on liver and intestinal fat content in milk-fed veal calves. Two experiments were performed at body weights (BW) of 80-160 kg (mean 120 kg; Exp. 1) and 160-240 kg (mean 200 kg; Exp. 2). In each experiment, 36 calves were allocated to one of six protein intake levels, at each of two energy intake levels. Digestible protein intakes ranged between 0.90 and 2.72 g nitrogen (N)/(kg BW(0.75) x d) in Exp. 1 and between 0.54 and 2.22 g N/(kg BW(0.75)x d) in Exp. 2. The two energy intake levels were kept constant on a protein-free basis and were 663 and 851 kJ/(kg BW(0.75) x d) in Exp. 1 and 564 and 752 kJ/(kg BW(0.75)x d) in Exp. 2. Blood samples were taken between 5 and 6h post-feeding at 14-d intervals until calves reached target BW, and liver fat mass was determined at slaughter. Urinary glucose excretion was quantified at 120 and 200 kg BW in Exps. 1 and 2, respectively. Increased protein-free energy intake increased plasma glucose concentrations and urinary glucose losses in 200 kg calves, but not in 120 kg calves. Increasing protein intake decreased plasma glucose, urinary glucose and plasma insulin in both experiments. Liver fat content decreased with increasing protein intake. In conclusion, long-term low-dietary protein intake increased hyperglycemia, hyperinsulinemia, glucosuria and hepatic steatosis in heavy milk-fed calves, likely associated with increased insulin resistance.     

Aminophylline Affects Glycemia Control and Increases Anaerobic Glycolysis in Horses during Incremental Exercise

A study was conducted on the effects of acute administration of aminophylline on physiological variables in purebred Arabian horses submitted to incremental exercise test. Twelve horses were submitted to two physical tests separated by a 10-day interval in a crossover study. These horses were divided into two groups: control (C, n = 12) and aminophylline (AM, n = 12). The drug at 10 mg/kg body weight or saline was given intravenously, 30 minutes before the incremental exercise test. The treadmill exercise test consisted of an initial warmup followed by gradually increasing physical exigency. Blood samples were assayed for lactic acid, glucose, and insulin. Maximal lactic acidemia was greater (P = .0238) in the AM group. Both V₂ and V₄ (velocities at which lactate concentrations were 2 and 4 mmol/L, respectively) were reduced in the AM group by 15.85% (P = .0402) and 17.76% (P = .0109), respectively. At rest as well as at 4 minutes, insulinemia was greater in the AM group (P = .0417 and .0393). Glycemia was statistically lower in the AM group at times 8 (P = .0138) and 10 minutes (P = .0432). Use of aminophylline in horses during incremental exercise does not seem to be beneficial, because this drug has a tendency to cause hypoglycemia and to increase dependence on anaerobic glucose metabolism.     

Effect of miR-7-5p targeting Itch gene on insulin resistance model of HepG2 cells

AIM:To preliminarily explore the relationship between microRNA-7-5p (miR-7-5p) and Itch gene and their relationship with insulin resistance by establishing insulin resistance model of HepG2 cells in vitro for detecting differential expression of miR-7-5p and its predicted target gene Itch in the state of insulin resistance. METHODS:The insulin resistance model of HepG2 cells was induced by suitable concentration of plamitic acid. The possible target genes and the associated signaling pathways of miR-7-5p were predicted based on bioinformatic analysis. The expression levels of miR-7-5p and Itch were detected by RT-qPCR and Western blot in the HepG2 cells with insulin resistance. RESULTS:The HepG2 cell model of insulin resistance was successfully induced by treatment with 0.25 mmol/L palmitic acid for 24 h. Compared with negative control group, the expression level of miR-7-5p detected by RT-qPCR in insulin resistance group was significantly decreased (P<0.01). Bioinformatic analysis showed that a considerable number of target genes of miR-7-5p were enriched in the ubiquitin proteasome system. Among them, E3 ubiquitin ligase Itch gene was the most relevant target gene to insulin resistance. The results of Western blot showed that the protein expression of Itch was up-regulated in the HepG2 cells under insulin resistance (P<0.01). CONCLUSION:miR-7-5p may be involved in the pathophysiological process of insulin resistance, which may directly or indirectly affect the normal transduction of insulin signaling pathway by targeting Itch gene.     

Insulin sensitivity and glucose dynamics during pre-weaning foal development and in response to maternal diet composition

Nutritional management of animals during pregnancy can affect glucose and insulin dynamics in the resulting offspring through influences on fetal development. Additionally, high starch feeding in mature horses is associated with reduced insulin sensitivity and an increased risk for diseases such as obesity and laminitis. However, no study has yet evaluated the effect of feeding a high starch diet to pregnant mares on glucose and insulin dynamics in their offspring. Twenty late-gestation mares maintained on pasture were provided two-thirds of digestible energy requirements from isocaloric, isonitrogenous low starch (LS, n = 10) or high starch (HS, n = 10) feed. Their foals were assessed with an insulin-modified frequently sampled intravenous glucose tolerance test at 5, 40, 80, and 160 d of age. Baseline glucose concentrations, insulin sensitivity, and insulin-independent glucose clearance in 5-d foals were all greater than values observed in mature horses and declined towards mature values as foals reached 160 d of age. Baseline glucose concentrations were all within normal range, but higher in foals born from HS mares through 80 d of age. Insulin sensitivity was not different between dietary groups until a trend for lower insulin sensitivity in HS foals emerged at 160 d of age. These data are the first to characterize decreasing insulin sensitivity and glucose tolerance in Thoroughbred foals from 5 to 160 d of age. This study also presents the first data examining glucose and insulin dynamics in developing foals in response to maternal high starch diet.     

Correlation of Plasma Insulin Concentration with Laminitis Score in a Field Study of Equine Cushing's Disease and Equine Metabolic Syndrome

This study aimed to investigate endocrinologic test values and the response to treatment of two commonly encountered causes of endocrinopathic laminitis, equine Cushing's disease (ECD) and equine metabolic syndrome (EMS), in a veterinary practice setting. In particular, the study aimed to determine whether insulin concentration correlated to the severity of clinical laminitis in horses with EMS or ECD. Twenty-five horses were included in the study and assigned to one of three groups: ECD (n = 6), EMS (n = 10), and controls (n = 9). Blood samples were collected at an initial visit and then at regular intervals for the next 12 months. Plasma concentrations of adrenocorticotropin (ACTH), cortisol, and insulin and serum concentrations of glucose and total thyroxine (T4) were obtained. Horses with ECD had significantly higher plasma ACTH concentrations than EMS horses or controls. Horses with EMS and ECD both had significantly higher plasma insulin concentrations than control horses, which was correlated with the Obel grade of laminitis (r = 0.63). After treatment, there was a trend for a reduction in plasma ACTH concentration in horses with ECD. A program of diet and exercise for horses with EMS resulted in reductions in both plasma insulin concentrations and bodyweight, which was variable, depending on the individual. There was a significant correlation between the change in plasma insulin concentration and Obel grade of laminitis (r = 0.69). This study has highlighted the importance of baseline plasma insulin concentration as a potential indicator of the susceptibility of horses to laminitis and the response to a program of diet and exercise.     

Oral glucose leads to a differential response in glucose,insulin, and GLP-1 in lean versus obese cats

The response to oral glucose was examined in 10 obese and 9 lean age-matched, neutered cats. In all cats, oral administration of 2 g/kg glucose was followed by a prompt increase in glucose, insulin, and glucagon-like peptide (GLP)-1. There were significant differences between lean and obese cats in the areas under the curve for glucose, insulin, and GLP-1. However, the responses were variable, and a clear distinction between individual lean and obese cats was not possible. Therefore, this test cannot be recommended as a routine test to examine insulin resistance in individual cats as it is used in people. A further disadvantage for routine use is also the fact that this test requires gastric tubing for the correct administration of the glucose and associated tranquilization to minimize stress and that it was associated with development of diarrhea in 25% of the cats. GLP-1 concentrations were much lower in obese than lean cats. The low GLP-1 concentrations in obese cats might indicate a contribution of GLP-1 to the lower insulin sensitivity of obese cats, but this hypothesis needs to be further investigated.     

Metabolic adaptations to heat stress in growing cattle

To differentiate between the effects of heat stress (HS) and decreased dry matter intake (DMI) on physiological and metabolic variables in growing beef cattle, we conducted an experiment in which a thermoneutral (TN) control group (n = 6) was pair fed (PF) to match nutrient intake with heat-stressed Holstein bull calves (n = 6). Bulls (4 to 5 mo old, 135 kg body weight [BW]) housed in climate-controlled chambers were subjected to 2 experimental periods (P): (1) TN (18 °C to 20 °C) and ad libitum intake for 9 d, and (2) HS (cyclical daily temperatures ranging from 29.4 °C to 40.0 °C) and ad libitum intake or PF (in TN conditions) for 9 d. During each period, blood was collected daily and all calves were subjected to an intravenous insulin tolerance test (ITT) on day 7 and a glucose tolerance test (GTT) on day 8. Heat stress reduced (12%) DMI and by design, PF calves had similar nutrient intake reductions. During P1, BW gain was similar between environments and averaged 1.25 kg/d, and both HS and PF reduced (P < 0.01) average daily gain (-0.09 kg/d) during P2. Compared to PF, HS decreased (P < 0.05) basal circulating glucose concentrations (7%) and tended (P < 0.07) to increase (30%) plasma insulin concentrations, but neither HS nor PF altered plasma nonesterified fatty acid concentrations. Although there were no treatment differences in P2, both HS and PF increased (P < 0.05) plasma urea nitrogen concentrations (75%) compared with P1. In contrast to P1, both HS and PF had increased (16%) glucose disposal, but compared with PF, HS calves had a greater (67%; P < 0.05) insulin response to the GTT. Neither period nor environment acutely affected insulin action, but during P2, calves in both environments tended (P = 0.11) to have a blunted overall glucose response to the ITT. Independent of reduced nutrient intake, HS alters post-absorptive carbohydrate (basal and stimulated) metabolism, characterized primarily by increased basal insulin concentrations and insulin response to a GTT. However, HS-induced reduction in feed intake appears to fully explain decreased average daily gain in Holstein bull calves.