Felix H. Schmidt

RESPIRATION OF THE β-CELLS IN THE PRESENCE OF SULFONYLUREAS

SUMMARY The hypoglycemic sulfonylureas, tolbutamide, and glibenclamide (HB 419) were found to stimulate the in vitro oxygen consumption of isolated pancreatic islets from obese-hyperglycemic mice. The respiratory rate of the islets increased with the concentration of HB 419 in the range 0.001–0.1 μg/ml, but it did not exceed 120% of the endogenous respiration. In an incubation medium containing glucose at a high concentration (3 mg/ml) the oxygen uptake was slightly inhibited by addition of either tolbutamide or HB 419. Addition of these drugs strongly inhibited the oxygen uptake of islets incubated in the presence of l -leucine. The oxidative decarboxylation of leucine-1-14C was also depressed by the addition of tolbutamide. The oxidation of d -glucose-U-14C remained unaffected when tolbutamide was added to islets incubated in a medium containing 3 mg/ml of glucose. The results are considered representative for the β-cells since this cell type comprises over 90% of the endocrine pancreas of obese hyperglycemic mice. The observations support the view that sulfonylureas stimulate the endogenous substrate oxidation and inhibit the degradation of leucine in the β-cells.

Morning Enzymatic Activity of DPP-4 Is Differentially Altered by Sleep Loss in Women and Men

No study to date has investigated whether the activity of circulating dipeptidyl peptidase 4 (DPP-4) is affected by sleep loss. DPP-4 is an enzyme that catalyzes a variety of important physiological processes in humans by cleavage of, e.g., the incretin hormones glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (1). Both chronic sleep loss and an increased activity of DPP-4 have been implicated in the development of several diseases, including type 2 diabetes (1–4). Twenty-five normal-weight healthy adults (aged 18–28 years; 13 women, using oral monophasic contraceptives) participated in two in-laboratory experimental conditions separated by about 1 week: one night of regular sleep (scheduled 2230–0630) and one night of total sleep loss, in a counterbalanced order. In the morning (∼0730), fasting blood samples were taken to measure the enzymatic activity of DPP-4, as previously described (3). The effects of sleep loss on DPP-4 activity were examined by using a linear mixed model (restricted maximum likelihood method; scaled identity as covariance matrix) with the fixed factors experimental condition (sleep/total sleep deprivation) and sex (women/men), as well as their interaction. All participants gave written informed consent, and the study was approved by the regional ethics review board …