Influence of Endogenous Insulin Secretion on Splanchnic Glucose and Amino Acid Metabolism in Man
Philip Felig,John Wahren +1 more
TLDR
Inhibition of hepatic glucose production associated with glucose infusion and large increments in insulin levels occurs in the absence of a decrease in the concentration of circulating gluconeogenic substrate, suggesting an hepatic rather than peripheral effect.Abstract:
Splanchnic exchange of glucose, 20 individual amino acids, lactate, and pyruvate was studied in normal subjects in the postabsorptive state and after stimulation of endogenous insulin secretion by infusion of glucose at two dose levels. In the basal state, mean splanchnic glucose production was 3.4 mg/kg per min. A net uptake of lactate, pyruvate, and nine amino acids was observed, with alanine accounting for half of the total splanchnic-amino acid extraction.
Infusion of glucose at 25 mg/kg per min for 20 min resulted in a fivefold increase in arterial insulin levels and in reversal of splanchnic glucose balance to a net uptake. Splanchnic uptake of alanine, glycine, phenylalanine, lactate, and pyruvate fell by 30-60% due to a reduction in fractional extraction of these substrates, inasmuch as their arterial concentrations did not decline.
Administration of glucose at 2 mg/kg per min for 45 min resulted in a 19 mg/100 ml increase in arterial glucose concentration and a doubling of arterial insulin levels. Despite the small increment in insulin, hepatic glucose production fell by 85%. Splanchnic exchange of amino acids, lactate, and pyruvate was unaltered. Estimated total glucose utilization during the infusion was no greater than in the basal state, indicating lack of stimulation of peripheral glucose uptake.
It is concluded that: (a) inhibition of hepatic glucose production associated with glucose infusion and large increments in insulin levels occurs in the absence of a decrease in the concentration of circulating gluconeogenic substrate, suggesting an hepatic rather than peripheral effect; (b) the liver is the primary target organ whereby glucose homeostasis is achieved with small increments in insulin; (c) the relatively greater sensitivity of the liver's response to insulin as compared with an effect of insulin on the peripheral tissues, may be a consequence of the higher levels of endogenous insulin in portal as compared with peripheral blood.read more
Citations
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Effects of insulin on peripheral and splanchnic glucose metabolism in noninsulin-dependent (type II) diabetes mellitus.
TL;DR: The results emphasize the importance of the peripheral tissues in the disposal of infused glucose and indicate that muscle is the most important site of the insulin resistance in NIDD.
Journal ArticleDOI
Dose-response characteristics for effects of insulin on production and utilization of glucose in man
TL;DR: The above dose-response relationships indicate that in man glucose production is more sensitive to changes in plasma insulin concentration than is glucose utilization; both hepatic and peripheral tissues may contain "spare" insulin receptors; and relatively minor changes in Plasma insulin concentration or insulin receptor function can cause appreciable alterations in glucose metabolism.
Journal ArticleDOI
The glucose-alanine cycle.
TL;DR: A glucose-alanine cycle in which alanine is formed peripherally by transamination of glucose-derived pyruvate and transported to the liver where its carbon skeleton is reconverted to glucose is suggested.
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Glucose metabolism during leg exercise in man
J. Wahren,J. Wahren,Philip Felig,Philip Felig,Gunvor Ahlborg,Gunvor Ahlborg,Lennart Jorfeldt,Lennart Jorfeldt +7 more
TL;DR: It is concluded that blood glucose becomes an increasingly important substrate for muscle oxidation during prolonged exercise of this type and peripheral glucose utilization increases in exercise despite a reduction in circulating insulin levels.
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Management of Hyperglycemic Crises in Patients With Diabetes
Abbas E. Kitabchi,Guillermo E. Umpierrez,Mary Beth Murphy,Eugene J. Barrett,Robert A. Kreisberg,John I. Malone,Barry M. Wall +6 more
TL;DR: Treatment of patients with DKA and HHS uses significant health care resources, which increases health care costs.
References
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TL;DR: It is concluded that the marked decrease in plasma alanine is due to augmented and preferential splanchnic utilization of this amino acid in early starvation resulting in substrate depletion and is an important component of the regulatory mechanism whereby hepatic gluconeogenesis is diminished and protein catabolism is minimized in prolonged fasting.
Journal ArticleDOI
Alanine: Key Role in Gluconeogenesis
TL;DR: Of 20 amino acids measured, alanine is the principal amino acid released by forearm muscle of man, in accord with its being the Principal amino acid extracted by liver for gluconeogenesis.