Reduced Insulin Response in Diabetes - a Quantitative or a Qualitative Problem?

Abstract

The lacking or reduced insulin response to glucose infusion is typical of diabetes mellitus. Nevertheless it is possible to verify a significant increase of the serum insulin level in maturity onset diabetics following tolbutamide of glucagon injection when reaction to oral glucose administration is missing. We examined whether it is possible to ob ta in a stimulation of insulin secretion by maximum increase of the blood glucose level by intravenous administration of glucose. For this purpose 9 diabetic patients have been studied. The patients received 0.75 g glucose per kg of body weight initial-Iy and therafter an infusion of 30 mg glucose per kg of body weight per minute during 30 minutes. Despite the blood glucose increase up to 1000mg/100 ml under intravenous infusion no stimulation of insulin secretion by the glucose took place. The same patients showed a significant insulin increase after stimulation with tolbutamide or glucagon. However, this response has been observed in patients also in cases where the oral stimulation with 100 g glucose did not result in any secretion whatever. This type of insulin secretion probably results from a completc alteration of the glucose receptor in respect of stimulation with glucose. ToLbutamide and glucagon rcceptors seem to be intact.

Insulin Secretion in Type II Diabetics: In Vivo and in Vitro Investigation1)

“…Concerning the second question whether the impaired insulin response to an in vivo glucose load reflects a quantitative reduction of beta cell sensitivity or a qualitatively different action we concluded from our results that the disorder of beta cell function can oniy be explained as a qualitative alteration of control mechanisms (Lohmann et al, 1977;Verlohren, 1981). This is also verified by the repeated study of insulin responses during a prolonged period after the onset of the disease.…”

Prevalence of residual B cell function and its metabolic consequences in Type 1 (insulin-dependent) diabetes

“…Also, during insulin-induced hypoglycaemia, B cells were sensitive to changes in glucose below the normal range [63]. On the other hand, it has been reported that B cells failed to respond to glucose concentrations up to 56 mmol/1 [11, 18,26,64,65]; however, they did respond to arginine [64], tolbutamide [18] and glucagon [18,651, suggesting a decrease in glucose sensitivity.…”

IRI-Secretion in MOD with and without SU (5 Year Control)

“…The insulin secretion in MOD is characterized by a lacking or delayed response to glucose, but a significant reaction to other stimuli such as sulfonylureas (SU) or glucagon (Lohmann, Ellorhaoui and Verlohren 1977). The question is still unanswered whether this reaction is only a stage in the course of disease or whether it is a constant state.…”