Glucose effectiveness assessed under dynamic and steady state conditions. Comparability of uptake versus production components.

Abstract

Glucose tolerance is determined by both insulin action and insulin-independent effects, or "glucose effectiveness," which includes glucose-mediated stimulation of glucose uptake (R d ) and suppression of hepatic glucose output (HGO). Despite its importance to tolerance, controversy surrounds accurate assessment of glucose effectiveness. Furthermore, the relative contributions of glucose's actions on R d and HGO under steady state and dynamic conditions are unclear. We performed hyperglycemic clamps and intravenous glucose tolerance tests in eight normal dogs, and assessed glucose effectiveness by two independent methods. During clamps, glucose was raised to three successive 90-min hyperglycemic plateaus by variable labeled glucose infusion rate; glucose effectiveness (GE) was quantified as the slope of the dose-response relationship between steady state glucose and glucose infusion rate (GE CLAMP (

Glucose-induced suppression of endogenous glucose production: dynamic response to differing glucose profiles

“…Uptake via hepatic GLUT2 transporters and phosphorylation by glucokinase appear to be important, because glucokinase deficiency decreases (14,32) and overexpression increases (23) hepatic glycogen synthesis. We (22) as well as other investigators (2,20) have shown that, in the presence of basal insulin concentrations, an increase in glucose concentrations within the physiological range results in linear suppression of EGP measured after 2-3 h of sustained hyperglycemia. The present data extend these observations by showing that the hepatic response to glucose is rapid both when glucose concentration is rising and when it is falling.…”

“…These data demonstrate that, in the presence of a constant basal insulin concentration, changes in glucose within the physiological range rapidly and reciprocally regulate EGP. glucose effectiveness; glucose turnover ENDOGENOUS GLUCOSE PRODUCTION (EGP) is regulated by plasma glucose and insulin concentrations (2,11,12,22,25,27). In the presence of a constant glucose concentration, insulin suppresses glucose production by both direct and indirect mechanisms (11).…”

“…In the presence of constant insulin concentrations, clamping glucose at a progressively higher concentration results in a progressive decrease in steady-state rates of EGP (2,20,22). Furthermore, EGP decreases when glucose concentration is increased in a pattern mimicking that commonly observed following ingestion of a carbohydrate-containing meal (5).…”

Glucose-mediated glucose disposal in insulin-resistant normoglycemic relatives of type 2 diabetic patients.

“…Glucose-mediated glucose disposal is an important factor controlling glucose tolerance (16,17), but which metabolic pathways are involved is uncertain (18)(19)(20). Acute hyperglycemia itself is known to enhance peripheral glucose uptake (19-24) associated with enhanced glucose oxidation and glu-cose storage (GS) (18)(19)(20)24) and to suppress hepatic glucose production (HGP) (19)(20)(21)(22)(23)25,26).…”

“…However, the estimation of S g may be influenced by the extent of the acute insulin secretory response, i.e., the lower the first-phase insulin response, the lower the S g (11-13). Concern has also been expressed as to whether the minimal model technique using unlabeled glucose accurately measures S g (14,15).Glucose-mediated glucose disposal is an important factor controlling glucose tolerance (16,17), but which metabolic pathways are involved is uncertain (18)(19)(20). Acute hyperglycemia itself is known to enhance peripheral glucose uptake (19-24) associated with enhanced glucose oxidation and gluFrom the Diabetes Research Centre…”