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1 Division of Endocrinology and Diabetes, Keck School of Medicine, University of Southern California, Los Angeles, California 90089; 2 Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905; 3 Department of Endocrinology, University of Aarhus, 8000-C Aarhus, Denmark; and 4 Division of Endocrinology and Metabolism, University of Virginia, Charlottesville, Virginia 22908
Impaired
insulin secretion in type 2 diabetes is characterized by decreased
first-phase insulin secretion, an increased proinsulin-to-insulin molar
ratio in plasma, abnormal pulsatile insulin release, and heightened
disorderliness of insulin concentration profiles. In the present study,
we tested the hypothesis that these abnormalities are at least partly
reversed by a period of overnight suspension of 
-cell secretory
activity achieved by somatostatin infusion. Eleven patients with type 2 diabetes were studied twice after a randomly ordered overnight infusion
of either somatostatin or saline with the plasma glucose concentration
clamped at ~8 mmol/l. Controls were studied twice after overnight
saline infusions and then at a plasma glucose concentration of either 4 or 8 mmol/l. We report that in patients with type 2 diabetes,
1) as in nondiabetic humans, insulin is secreted in discrete
insulin secretory bursts; 2) the frequency of pulsatile
insulin secretion is normal; 3) the insulin pulse mass is
diminished, leading to decreased insulin secretion, but this defect can
be overcome acutely by -cell rest with somatostatin; 4)
the reported loss of orderliness of insulin secretion, attenuated
first-phase insulin secretion, and elevated proinsulin-to-insulin molar
ratio also respond favorably to overnight inhibition by somatostatin.
The results of these clinical experiments suggest the conclusion that
multiple parameters of abnormal insulin secretion in patients with type
2 diabetes mechanistically reflect cellular depletion of immediately
secretable insulin that can be overcome by -cell rest.
pulsatile insulin secretion; hyperglycemia; orderliness; C-peptide; somatostatin; proinsulin
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