Diabetes, Vol 35, Issue 7 776-784, Copyright © 1986 by American Diabetes Association
Relative importance of first- and second-phase insulin secretion in glucose homeostasis in conscious dog. II. Effects on gluconeogenesis
KE Steiner, SM Mouton, PE Williams, WW Lacy and AD Cherrington
The normal pancreatic response to an exogenous glucagon infusion is a
biphasic release of insulin. In our study the ability of each component of
insulin release to counter the effects of the glucagon on gluconeogenesis
and alanine metabolism was assessed by mimicking first- and/or second-phase
insulin release with infusions of somatostatin and intraportal insulin.
When a fourfold increase in glucagon was brought about in the presence of
fixed basal insulin release, there was a large increase in overall glucose
production and gluconeogenesis. The increase in the conversion of
[14C]alanine into [14C]glucose (169 +/- 42%, P less than .05) was
accompanied by an increase in the fractional extraction of alanine by the
liver (FEA 0.32 +/- 0.06 to 0.66 +/- 0.10, P less than .05) and net hepatic
alanine uptake (NHAU 2.97 +/- 0.45 to 4.61 +/- 0.48 mumol . kg-1 . min-1, P
less than .05). Simulated first-phase insulin release had no effect on the
ability of glucagon to increase FEA (0.32 +/- 0.03 to 0.66 +/- 0.03, P less
than .05) or NHAU (3.69 +/- 0.80 to 5.10 +/- 0.69 mumol . kg-1 . min-1, P
less than .05) but did limit the increase in overall gluconeogenic
conversion (114 +/- 37%). Second-phase insulin release had no effect on
either the glucagon-induced increase in FEA (0.35 +/- 0.08 to 0.73 +/-
0.04) or NHAU (3.35 +/- 0.92 to 5.13 +/- 0.85 mumol . kg-1 . min-1) but
completely inhibited the increase in overall gluconeogenic
conversion.(ABSTRACT TRUNCATED AT 250 WORDS)