Influence of a 60-hour fast on insulin-mediated splanchnic and peripheral glucose metabolism in humans.

Abstract

A brief period of starvation (2-3 d) depletes the hepatic glycogen stores but results in only a limited reduction of the muscle glycogen depots. In this situation insulin resistance contributes to the glucose intolerance, but it is not known which tissue or tissues are responsible for the decreased insulin sensitivity. The present study was therefore undertaken to examine the influence of a 60-h fast on insulin sensitivity in splanchnic and peripheral tissues in normal humans. Euglycemic (95 mg/dl) 1-mU insulin and hyperglycemic (215-225 mg/dl) glucose clamp studies were conducted for 2 h in overnight (12 h) and prolonged (60 h) fasted nonobese subjects. Splanchnic exchange of glucose and gluconeogenic precursors was measured using the hepatic vein catheter technique.During the euglycemic clamp, insulin infusion resulted in similar steady state insulin levels in 60-h and 12-h fasted subjects (73±7 vs. 74±5 ttU/ml). Total glucose disposal was reduced by 45% after 60 h of fasting (4.0±03 vs. 7.6±1.1 mg/kg per min, P < 0.05) and the splanchnic glucose balance reverted from a net release in the basal state (12 h fast, -1.7±0.2, and 60-h fast, -0.9±0.1 mg/kg per min, P < 0.01) to a net uptake during the clamps that was similar after 60 h and 12 h of fasting (0.6±0.1 vs. 0.6±0.2 mg/kg per min).During the hyperglycemic clamp, insulin levels rose rapidly in all subjects. In the 12-h fasted group this rise was followed by a further gradual one, reaching significantly higher values than in 60-h fasted subjects during the second hour (67±15 vs. 25±2 AU/ml, P < 0.05). Total glucose disposal was lower, though not significantly so, after the 60-h fast (2.6±0.4 vs. 5.4±13 mg/kg per min, 0.05 < P < 0.10), and as with the euglycemic clamp, the splanchnic glucose balance was altered from a basal net release to a net uptake during the clamp (1.3±0.2 vs. 1.1±0.2 mg/kg per min).After an overnight fast, splanchnic lactate uptake fell and the arterial lactate concentration rose in response to both hyperglycemia and hyperinsulinemia, whereas these variables were unchanged in the 60-h fasted subjects during both types of clamp studies. We conclude that peripheral tissues are predominantly responsible for the insulin resistance seen in starvation. In contrast, net splanchnic glucose uptake in response to hyperinsulinemia and/or hyperglycemia remains unchanged during starvation, despite the depletion of the hepatic glycogen stores.

Impact of portal glucose delivery on glucose metabolism in conscious, unrestrained mice

“…This is consistent with recent studies in the mouse in which overnight fasting augmented insulin action as assessed by euglycemic hyperinsulinemic clamps (1,14). In contrast, extended fasting (60 and 96 h) induces insulin resistance in humans (3,11).…”

Mechanism of impaired glucose-potentiated insulin secretion in diabetic 90% pancreatectomy rats. Study using glucagonlike peptide-1 (7-37).

“…Insulin secretion also improves (30), although the mechanism is unclear. It was recently reported that a 4-d fast enhanced insulin secretion in NIDDM (16), which contrasts with the reduced insulin secretory capacity that occurs normally (31). The current study investigated the mechanism of the same finding in 90% Px diabetic rats.…”

β-Hydroxybutyrate inhibits insulin-mediated glucose transport in mouse oxidative muscle

“…Short-term starvation is another condition associated with elevated rates of FFA oxidation and marked elevations in blood ketone body levels (8). A common denominator between uncontrolled diabetes and starvation is insulin resistance (6,9,10), defined as diminished glucose transport by skeletal muscle in response to insulin. The elevated levels of FFA during uncontrolled diabetes and starvation can contribute to the insulin resistance (27).…”