Insulin production rate, hepatic insulin retention and splanchnic carbohydrate metabolism after oral glucose ingestion in hyperinsulinaemic Type 2 (non-insulin-dependent) diabetes mellitus

Abstract

To differentiate peripheral and hepatic insulin resistance in hyperinsulinaemic overweight Type 2 (non-insulin-dependent) diabetic patients (n = 17; 143 +/- 4% ideal body weight; mean +/- SEM) arterial concentrations and splanchnic exchange of glucose, pyruvate, lactate, non-esterified fatty acids, beta-hydroxybutyrate and acetoacetate, as well as the insulin production rate, were determined before and during oral glucose loads of 25 g or 100 g. Insulin production rate, hepatic insulin retention and splanchnic exchange of glucose and metabolites were estimated by means of the hepatic venous catheter technique. In the basal state insulin production rate was greater in overweight Type 2 diabetic patients (2.57 +/- 0.28 pmol.kg-1. min-1) than in healthy control subjects (1.68 +/- 0.17 pmol.kg-1.min-1; p less than 0.01). After ingestion of 25 g glucose, the cumulative insulin production rate exceeded normal values (p less than 0.05), but was below normal with 100 g glucose (p less than 0.01). Relative insulin trapping by the splanchnic bed in the diabetic patients was 54 +/- 3%, not different from normal. Following a 100 g glucose load, splanchnic insulin retention fell by 20% in the patients, and less consistently so in healthy controls. Splanchnic glucose output was normal in the diabetic patients both in the basal state and after glucose ingestion although the induced arterial blood glucose levels were greater in the diabetic patients than in control subjects (p less than 0.005). Splanchnic output of pyruvate (p less than 0.025), lactate (p less than 0.01), and beta-hydroxybutyrate (p less than 0.005) were greater in the basal state in the diabetic patients than in healthy subjects. However, no difference in splanchnic exchange was seen between the two groups in their metabolites' respective response to glucose ingestion. These data suggest that obese hyperinsulinaemic Type 2 diabetic patients may represent a subgroup of diabetic patients with predominantly peripheral, but compensated hepatic, insulin resistance being associated with an increased basal insulin production rate which only exhausts after ingestion of a large glucose load.

Fatty acids, lipotoxicity and insulin secretion

“…In separate studies, initial stimulation followed by suppression of GSIS was noted [76] after perifusion of rat islets with 1 mmol/l palmitate (in the context of 3 % albumin), but under these conditions the inhibitory effect of the fatty acid was evident after only 2 h. Subsequent studies involving long-term exposure of rat islets to high concentrations of fatty acids [77,78] showed a consistent pattern, namely, an enhanced insulin secretion at low glucose concentrations, coupled with suppression of proinsulin biosynthesis, reduced insulin stores and an impaired ability of the beta cell to respond to a high glucose concentration. These are characteristic features of the beta-cell dysfunction in human Type II diabetes, as shown, for example in experiments in which obese Type II diabetic patients displayed enhanced insulin secretion in response to a small glucose load, but reduced insulin release when the glucose challenge was increased [79]. These features are also seen in the male Zucker Diabetic Fatty rat.…”

Insulin action during late pregnancy in the conscious dog

“…The shift from net hepatic lactate release to uptake is an indicator of the transition from the fed to the fasted state in the dog (29), as in the human (3,39). This raises the question whether the pregnant group should have been studied after a shorter period of fasting than the nonpregnant group in order for the groups to start from a more similar metabolic state.…”

11?-Hydroxysteroid dehydrogenase Type 1 in obesity and Type 2 diabetes

“…Type 2 diabetes is characterised by disturbed insulin secretion in addition to decreased insulin sensitivity [70,71]. In contrast to the well-known secondary hyperinsulinaemia in response to acute cortisol exposure in healthy subjects [72], glucocorticoids even in physiological concentrations directly inhibit insulin secretion from pancreatic islets in vitro and in vivo [10,73,74,75,76].…”