Dry period plane of energy: Effects on glucose tolerance in transition dairy cows.

Overfeeding energy in the dry period can affect glucose metabolism and the energy balance of transition dairy cows with potential detrimental effects on the ability to successfully adapt to early lactation. The objectives of this study were to investigate the effect of different dry cow feeding strategies on glucose tolerance and on resting concentrations of blood glucose, glucagon, insulin, nonesterified fatty acids (NEFA), and ß-hydroxybutyrate (BHB) in the peripartum period. Cows entering second or greater lactation were enrolled at dry-off (57 d before expected parturition) into 1 of 3 treatment groups following a randomized block design: cows that received a total mixed ration (TMR) formulated to meet but not exceed energy requirements during the dry period (n=28, controlled energy); cows that received a TMR supplying approximately 150% of energy requirements during the dry period (n=28, high energy); and cows that were fed the same diet as the controlled energy group for the first 28 d, after which the TMR was formulated to supply approximately 125% of energy requirements until calving (n=28, intermediate energy). Intravenous glucose tolerance tests (IVGTT) with rapid administration of 0.25 g of glucose/kg of body weight were performed 28 and 10d before expected parturition, as well as at 4 and 21 d after calving. Area under the curve for insulin and glucose, maximal concentration and time to half-maximal concentration of insulin and glucose, and clearance rates were calculated. Insulin resistance (IR) indices were calculated from baseline samples obtained during IVGTT and Spearman rank correlations determined between IVGTT parameters and IR indices. Treatment did not affect IVGTT parameters at any of the 4 time points. Correlation between IR indices and IVGTT parameters was generally poor. Overfeeding cows energy in excess of predicted requirements by approximately 50% during the entire dry period resulted in decreased postpartum basal plasma glucose and insulin, as well as increased glucagon, BHB, and NEFA concentrations after calving compared with cows fed a controlled energy diet during the dry period. In conclusion, overfeeding energy during the entire dry period or close-up period alone did not affect glucose tolerance as assessed by IVGTT but energy uptake during the dry period was associated with changes in peripartal resting concentrations of glucose, as well as postpartum insulin, glucagon, NEFA, and BHB concentrations.

Loss of coupling between calcium influx, energy consumption and insulin secretion associated with development of hyperglycaemia in the UCD-T2DM rat model of type 2 diabetes.

AIMS/HYPOTHESIS: Previous studies on isolated islets have demonstrated tight coupling between calcium (Ca(2+)) influx and oxygen consumption rate (OCR) that is correlated with insulin secretion rate (ISR). To explain these observations, we have proposed a mechanism whereby the activation of a highly energetic process (Ca(2+)/metabolic coupling process [CMCP]) by Ca(2+) mediates the stimulation of ISR. The aim of the study was to test whether impairment of the CMCP could play a role in the development of type 2 diabetes. METHODS: Glucose- and Ca(2+)-mediated changes in OCR and ISR in isolated islets were compared with the time course of changes of plasma insulin concentrations observed during the progression to hyperglycaemia in a rat model of type-2 diabetes (the University of California at Davis type 2 diabetes mellitus [UCD-T2DM] rat). Islets were isolated from UCD-T2DM rats before, 1 week, and 3 weeks after the onset of hyperglycaemia. RESULTS: Glucose stimulation of cytosolic Ca(2+) and OCR was similar for islets harvested before and 1 week after the onset of hyperglycaemia. In contrast, a loss of decrement in islet OCR and ISR in response to Ca(2+) channel blockade coincided with decreased fasting plasma insulin concentrations observed in rats 3 weeks after the onset of hyperglycaemia. CONCLUSIONS/INTERPRETATION: These results suggest that phenotypic impairment of diabetic islets in the UCD-T2DM rat is downstream of Ca(2+) influx and involves unregulated stimulation of the CMCP. The continuously elevated levels of CMCP induced by chronic hyperglycaemia in these islets may mediate the loss of islet function.

Leptin therapy in type 2 diabetes.

There is a pressing need for new effective therapeutic strategies for addressing the epidemic of type 2 diabetes. Leptin has been shown to reduce hyperglycaemia in rodent models of type 1 diabetes and has recently been shown to normalize fasting plasma glucose concentrations in a rodent model of polygenic obesity and type 2 diabetes. Overall, these findings suggest that leptin may be an effective therapeutic option for both type 1 and type 2 diabetes. However, short-term human clinical studies in overweight and obese patients with recently diagnosed type 2 diabetes have reported minimal efficacy of leptin administration to lower blood glucose levels. Herein, the role of leptin in the maintenance of glucose homeostasis and the potential use of leptin in the treatment of type 2 diabetes are discussed.