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

Am J Physiol. 1989 Aug;257(2 Pt 1):E241-6. doi: 10.1152/ajpendo.1989.257.2.E241.


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 micrograms/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 phase 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/min, 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 less than 0.01 vs. studies I and III) and remained incompletely suppressed even after 150 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Blood Glucose / metabolism*
  • C-Peptide / blood
  • Female
  • Glucagon / pharmacology*
  • Gluconeogenesis*
  • Glucose / metabolism*
  • Glucose Clamp Technique
  • Humans
  • Hyperglycemia / physiopathology*
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin / pharmacology
  • Insulin Secretion
  • Kinetics
  • Liver / metabolism*
  • Male
  • Reference Values


  • Blood Glucose
  • C-Peptide
  • Insulin
  • Glucagon
  • Glucose