Dose-response characteristics for effects of insulin on production and utilization of glucose in man

Abstract

To determine the dose-response characteristics for the effects of insulin on glucose production, glucose utilization, and overall glucose metabolism in normal man, 15 healthy subjects were infused with insulin for 8 h at sequential rates ranging from 0.2 to 5.0 mU.kg-1.min-1; each rate was used for 2 h. Glucose production and utilization were measured isotopically ([3-3H]glucose). Tissue insulin receptor occupancy was estimated from erythrocyte insulin binding. Glucose production was completely suppressed at plasma insulin concentrations of approximately 60 microunits/ml. Maximal glucose utilization (10-11 mg.kg-1.min-1) occurred at insulin concentrations of 200-700 microunits/ml. The concentration of insulin causing half-maximal glucose utilization (55 + 7 microunits/ml) was significantly greater than that required for half-maximal suppression of glucose production (29 +/- 2 microunits/ml, P less than 0.01). Maximal effects of insulin on glucose production and utilization occurred at plasma insulin concentrations causing 11 and 49% insulin receptor occupancy, respectively. The above dose-response relationships indicate that in man 1) glucose production is more sensitive to changes in plasma insulin concentration than is glucose utilization; 2) both hepatic and peripheral tissues may contain "spare" insulin receptors; and 3) relatively minor changes in plasma insulin concentration or insulin receptor function can cause appreciable alterations in glucose metabolism.

Nasal insulin changes peripheral insulin sensitivity simultaneously with altered activity in homeostatic and reward-related human brain regions

“…The absorption of small amounts of nasally delivered insulin into the peripheral circulation was not unexpected, having been noted in other studies [11,15,21]. A transient 20 % increase in plasma insulin as observed in our study at 30 min should be biologically active [22,23], regardless of whether it is of endogenous or exogenous origin. The drop in plasma glucose, however, was only slight, indicating that the effectiveness of insulin was impaired at the periphery.…”

Decreased glucose utilization during prolonged anaesthesia and surgery

“…Previous methods for assessing insulin resistance have depended on only one insulin dose or concentration and may underestimate or fail to demonstrate the presence of insulin resistance. 9 The euglycaemic insulin clamp test, introduced by Defronzo, 4 was utilized to estimate the tissue sensitivity to insulin. In this technique, plasma insulin concentration is increased acutely and maintained above 200 p,U.…”

Effects of nicotinic acid on insulin sensitivity and blood pressure in healthy subjects

“…22 Following this a primed constant infusion of human insulin (Actrapid HM, Novo-Nordisk, Sydney, Australia) was administered at a rate of 240 pmol/m 2 /min for 120 min to achieve circulating concentrations of insulin in the mid to high physiological range previously shown to completely suppress hepatic glucose output. 23 Blood samples were taken every 5 min from the arterialised line and blood glucose levels were immediately measured on a glucose analyser (Yellowsprings 1500 Sidekick D-Glucose Analyser, Yellow Springs Instrument Co., Yellow Springs, OH, USA). The exogenous glucose infusion was adjusted according to a standard algorithm in order to maintain the blood glucose at 4.5 mmol/L.…”