Influence of liver triglycerides on suppression of glucose production by insulin in men

Eunsook S. Jin, Magdalene Szuszkiewicz-Garcia, Jeffrey D. Browning, Jeannie D. Baxter, Nicola Abate, Craig R. Malloy

Research output: Contribution to journalArticle

Abstract

CONTEXT: The ability of insulin to suppress hepatic glucose production is impaired among subjects with increased intrahepatic triglycerides (IHTG). However, little is known about the roles of insulin on the supporting fluxes of glucose production among patients with fatty liver.

OBJECTIVE: To evaluate the effects of insulin on fluxes through the three potential sources of plasma glucose (glycerol, the citric acid cycle, and glycogen) among patients with fatty liver. Design, Settings, Participants, and Intervention: Nineteen men with a range of IHTG (∼0.5% to 23%) were studied after an overnight fast and during hyperinsulinemia using magnetic resonance spectroscopy and stable isotope tracers.

MAIN OUTCOME MEASURES: IHTG, gluconeogenesis from glycerol, gluconeogenesis from the citric acid cycle, glycogenolysis, and (13)C-labeled glucose produced from the citric acid cycle during hyperinsulinemia were measured.

RESULTS: Men with high IHTG had higher fluxes through all pathways contributing to glucose production during hyperinsulinemia, compared to men with low IHTG, but they had similar fluxes after the fast. Consequently, men with fatty liver had impaired insulin efficiency in suppressing total glucose production as well as fluxes through all three biochemical pathways contributing to glucose. The detection of glucose isotopomers with (13)C arising from [U-(13)C3]propionate ingested during hyperinsulinemia demonstrated continuous gluconeogenesis from the citric acid cycle in all subjects.

CONCLUSIONS: These findings challenge the concept that individual glucose production pathways are selectively dysregulated during hepatic insulin resistance. Overproduction of glucose during hyperinsulinemia in men with fatty liver results from inadequate suppression of all the supporting fluxes of glucose production in response to insulin.

Original languageEnglish (US)
Pages (from-to)235-243
Number of pages9
JournalThe Journal of clinical endocrinology and metabolism
Volume100
Issue number1
DOIs
StatePublished - Jan 1 2015

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Liver
Triglycerides
Insulin
Glucose
Hyperinsulinism
Citric Acid Cycle
Fatty Liver
Fluxes
Gluconeogenesis
Glycerol
Magnetic resonance spectroscopy
Glycogenolysis
Propionates
Glycogen
Isotopes
Insulin Resistance
Magnetic Resonance Spectroscopy
Plasmas

ASJC Scopus subject areas

  • Medicine(all)

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Influence of liver triglycerides on suppression of glucose production by insulin in men. / Jin, Eunsook S.; Szuszkiewicz-Garcia, Magdalene; Browning, Jeffrey D.; Baxter, Jeannie D.; Abate, Nicola; Malloy, Craig R.

In: The Journal of clinical endocrinology and metabolism, Vol. 100, No. 1, 01.01.2015, p. 235-243.

Research output: Contribution to journalArticle

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