Initiation of increased pancreatic islet growth in young normoglycemic mice (Umea +/?)

Pancreatic islets from obese hyperglycemic mice are large and contain a hig h proportion of normally functioning p-cells. We have previously shown that young obese mice have an elevated P-cell proliferation rate at 3 weeks of age. We now wanted to investigate possible factors involved in the initiati on of islet growth, including blood glucose, C peptide, glucagon-like pepti de-1, vasoactive intestinal polypeptide, and L-5-hydroxytryptophan, We foun d that the increased beta-cell proliferation on day 20 precedes the rise in blood glucose by 2 days. The islet cell proliferation, measured as the 5-b romo-2'-deoxyuridine labeling index, in 20-day-old lean mice, was Enhanced in a dose-dependent manner when glucagon-like peptide-1 or C peptide was in jected sc for 2 days. L-5-Hydroxytryptophan inhibited the proliferation. C Peptide also increased the islet cell labeling index during islet culture. We conclude that in addition to the effect of glucose, islet proliferation can be triggered by other factors involved in the physiological regulation of increased insulin release. Stimulation of islet proliferation may be rel ated to the actual release of insulin, and C peptide may function as a medi ator of such responses.