We assessed the effects of
insulin and normalization of
blood glucose on plasma levels of
somatostatin-like immunoreactivity (SLI) in patients with
noninsulin-dependent diabetes mellitus (
NIDDM). In one series of experiments, normalization of
blood glucose was achieved by Biostator-controlled feedback infusion of
insulin. This procedure reduced plasma SLI levels by 34% [from 17.1 +/- 2.1 (+/- SEM) to 11.3 +/- 1.9 pg/ml; P less than 0.05], concomitant with a significant reduction in plasma
glucagon and
C-peptide and an evanescent decrease in plasma gastric inhibitory
peptide (GIP) levels. An ensuing mixed meal elicited a rise in SLI that reached the same levels during infusion of
insulin as during uncontrolled
hyperglycemia; the incremental increase was, however, 45% higher (P less than 0.005) during
insulin infusion. Furthermore feedback
insulin infusion enhanced GIP and decreased
C-peptide responses, but did not affect the
glucagon response to the meal. To further evaluate the influence of
insulin of SLI levels, we compared the effects of normo- and
hyperglycemia during constant
hyperinsulinemia by varying the rate of
glucose infusion (
glucose clamping). Basal SLI levels decreased significantly only during the normoglycemic clamp. The SLI response to a meal was more pronounced during the normoglycemic than the hyperglycemic clamp. The patterns of
glucagon and GIP were similar during the two clamp conditions, while both basal and stimulated
C-peptide levels were lower during the normoglycemic clamp. To investigate the temporal relationship between changes in
blood glucose and SLI levels, patients were studied during a prolonged (270-min) period of normoglycemic clamp and fasting. After attaining normoglycemia, SLI levels continued to decline for 150 min, whereas
glucagon and GIP levels did not change. We conclude that in patients with
NIDDM,
insulin significantly lowers basal SLI levels if normoglycemia is concomitantly attained; this action of
insulin was partially dissociated from its
hypoglycemic action;
hyperglycemia per se inhibits a meal-induced SLI response, and
insulin effects on SLI are not secondary to changes in
glucagon or GIP levels.