Effect of loss of first-phase insulin secretion on hepatic glucose production and tissue glucose disposal in humans

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Abstract

To examine the importance of first-phase insulin secretion on total body glucose homeostasis, six normal subjects (age, 24 ± 1 yr; ideal body wt, 100 ± 1%) received three hyperglycemic (+75 mg/100 ml) clamp studies in combination with [3-3H]glucose: study I, 150 min hyperglycemic clamp; study II, hyperglycemic clamp plus somatostatin (6 μg/min) plus basal glucagon replacement (0.4 ng·kg-1·min-1) plus an insulin infusion designed to mimic only the second phase of insulin secretion; and study III, hyperglycemic clamp plus somatostatin plus basal glucagon plus an insulin infusion designed to mimic both the first and second phases of insulin secretion. Basal plasma C-peptide concentrations averaged 0.21 ± 0.01 pmol/ml in the three study protocols. In study I the plasma C-peptide response demonstrated an early burst within the first 10 min followed by a gradually increasing phase of C-peptide secretion that lasted until the end of the study. In studies II and III plasma C-peptide declined within the first 10 min after somatostatin was started and averaged 0.06 ± 0.01 and 0.05 ± 0.01 pmol/ml, respectively. Basal hepatic glucose production (2.3 ± 0.2 mg·kg-1·min-1) was suppressed by 90% at 20 min and remained suppressed thereafter in studies I and III. In contrast, in study II hepatic glucose production was inhibited by only 50% (1.1 ± 0.2 mg·kg-1·min-1) at 60 min (P < 0.01 vs. studies I and III) and remained incompletely suppressed even after 150 min. Total body glucose disposal averaged 5.3 ± 0.3, 5.9 ± 0.5, and 6.5 ± 0.5 mg·kg-1·min-1 in studies I, II, and III. In conclusion, the loss of first-phase insulin secretion causes a marked delay in the inhibition of hepatic glucose production but does not impair peripheral glucose disposal. This defect may contribute to the glucose intolerance observed in the early stages of types 1 and 2 diabetes mellitus, both of which are characterized by the loss of first-phase insulin secretion.

Original languageEnglish (US)
Pages (from-to)20/2
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume257
Issue number2
StatePublished - Jan 1 1989

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ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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