Insulin Control of Glucose Metabolism in Man

Abstract

A B S T R A C T Analyses of the control of glucose metabolism by insulin have been hampered by changes in blood glucose concentration induced by insulin administration with resultant activation of hypoglycemic counterregulatory mechanisms. To eliminate such mechanisms, we have employed the glucose clamp technique which allows maintenance of fasting blood glucose concentration during and after the administration of insulin. Analyses of six studies performed in young healthy men in the postabsorptive state utilizing the concurrent administration of [1'C] During the glucose clamp experiments plasma insulin levels reached a plateau of 95±8 /U/ml. Over the entire range of insulin levels studied, glucose losses were best correlated with levels of insulin in a slowly equilibrating insulin compartment of a three-compartment insulin model. A proportional control by this compartment on glucose utilization was adequate to satisfy the observed data. Insulin also rapidly decreased the endogenous glucose production to 33% of its basal level (0.58 mg/ kg per min), this suppression being maintained for at least 40 min after exogenous insulin infusion was terminated and after plasma insulin concentrations had returned to basal levels.The change in glucose utilization per unit change in insulin in the slowly equilibrating insulin compartment is proposed as a new measure for insulin sensitivity. This defines insulin effects more precisely than previously used measures, such as plasma glucose/plasma insulin concentration ratios.Glucose clamp studies and the modeling of the coupled kinetics of glucose and insulin offers a new and potentially valuable tool to the study of altered states of carbohydrate metabolism.

Insulin sensitivity, insulin secretion and glucose effectiveness in diabetic and non-diabetic cirrhotic patients

“…In keeping with earlier reports [38] we found a good correlation between the 6-19 rain Ko value and the incremental first phase insulin response to glucose in both control subjects (r = 0.873, p < 0.001) and the combined cirrhotic patient groups (r = 0.797, p < 0.001). It is unlikely that this relationship simply reflects the effect of insulin on peripheral tissues, as there is a substantial delay between an increase in plasma insulin and the effect of this increase on glucose disposal [20,21,39]. Although, there was a significant relationship between Ko and $6 in the control subjects and in the two cirrhotic groups combined, this was not as striking as the relationship between K~ and the incremental first phase insulin response to glucose.…”

“…The delay between a rise in plasma insulin and the effect of this rise on glucose metabolism [20,21,39] is thought to be due mainly to the time required to transport insulin into the interstitial space. In dogs the rate of glucose utilisation correlates better with changes in lymph insulin (thought to be representative of interstitial insulin) than with changes in plasma insulin concentration [42].…”

“…Briefly, the minimal model of glucose kinetics describes the relationship between serum insulin levels during the FSIGT and the decfine in the blood glucose concentration after i. v. glucose. The model assumes: (1) that glucose inhibits HGO and increases tissue glucose utilisation in proportion to its concentration in plasma [16][17][18][19]; (2) that insulin enhances these effects of glucose; and (3) that the effect of insulin to promote glucose disappearance from plasma depends on the concentration of insulin in a compartment remote from plasma [20,21]. These assumptions are represented by the following two equations of the minimal model:…”

Adipose tissue as a buffer for daily lipid flux

“…ranges of fatness [3,4,5]. Paradoxically, a deficiency of adipose tissue, as in lipodystrophy or lipoatrophy in humans [6,7] and rodents [8,9,10], is also associated with insulin resistance.…”

Administration of dexamethasone per os in finishing bulls. I. Effects on productive traits, meat quality and cattle behaviour as indicator of welfare

“…During the same period, dexamethasone, acting as endogenous glucocorticoid, and hyperglycaemia might have promoted insulin production by the pancreatic b cells. The reduction of glycaemia observed during the last part of the experiment in the bulls treated is likely due to the hypoglycaemic role of insulin (Insel et al, 1975;Mori et al, 2004). The organism's response to prolonged oral administration of a low dosage of dexamethasone in terms of the hepatic synthesis of glucose is immediate, whereas response in terms of insulin production seems to require a longer adaptation period.…”