Diurnal Variations of Serum Insulin, Total Glucagon, Cortisol, Glucose and Free Fatty Acids in Normal and Diabetic Subjects before and after Treatment with Chlorpropamide

Abstract

Serum levels of insulin (IRI), total glucagons (GLI), cortisol, glucose and free fatty acids were measured in 14 normal subjects and in 6 diabetic patients. All of them were hospitalized, but not con- , fined to bed and were given 3 daily meals of identical carbohydrate, fat and protein content. Blood samples were collected through an indwelling venous catheter at hourly intervals for 72 h. In addition, three 15-min samples were collected after each meal. The study was repeated about 1 month later, during the last 3 days of a period of chlorpropamide treatment. The results confirm the existence of a diurnal cycle in serum cortisol in normal and diabetic subjects. Diurnal variations in the postprandial glucose response of normal subjects and in the postprandial IRI response of diabetic patients were observed, but they may have been drug-induced. Chlorpropamide treatment had no significant effects in normal subjects, but was followed by a decrease in the concentration of serum GLI and by an increase in the fasting levels of IRI and in the IRI response to meals in diabetic patients. These changes may explain the restraining effect that the drug had on postprandial hyperglycemia. The results of our experiments suggest that the therapeutic effect of chlorpropamide in adult onset diabetic patients may be due to a combination of an increased release of insulin and a decreased release of total gucagon in response to the ingestion of food. The difference in the response of normal and diabetic subjects to prolonged chlorpropamide treatment remains unexplained, but may account for some of the conflicting reports on the effects of sulfonylurea derivatives on insular function.

Dapagliflozin stimulates glucagon secretion at high glucose: experiments and mathematical simulations of human A-cells

“…Reported results on glucagon secretion vary considerably. For example sulfonylureas have been reported to increase, decrease and to have no effect on secretion 15 42 43 44 . Also results with the KATP-channel opener diazoxide vary, and the stimulatory effect of low dose diazoxide on secretion in the presence of high glucose could not be reproduced in a study by Cheng-Zue et al .…”

Diurnal Variations of Food Consumption, Plasma Glucose and Plasma Insulin Concentrations in Lean and Obese Hyperglycaemic Mice

“…An appreciation of these variations has improved both the diagnosis and treat ment of disorders of carbohydrate metabolism (Roberts, 1968;Sensi et al, 1973;Goschke et al, 1974;Loreti et al, 1974;Walsh et al, 1974).…”

Tolbutamide-induced changes of the DNA, protein and insulin content and the secretory activity of isolated rat pancreatic islets

“…The lowered sensitivity of the B-cell insulin releasing mechanism induced by prolonged treatment with tolbutamide may, therefore, be partially effected by an interference with the enzymatic system generating and inactivating cyclic adenosine monophosphate. However, studies on the effect of sulfonylureas on islet tissue should consider that normal and diabetic islet tissue might act differently towards these agents, as recently suggested [43].…”