A role of nicotinamide-induced increase in pancreatic beta-cell mass on blood glucose control after discontinuation of the treatment in partially pancreatectomized OLETF rats.
Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of NIDDM, is normoglycemic at a young age. However, they become hyperglycemic, even at a young age as a result of a 70% pancreatectomy, which is associated with insufficient proliferation of beta-cells. Administration of nicotinamide ameliorates the sustained hyperglycemia by increasing beta-cell proliferation. In order to further understand its mode of action, we studied how long nicotinamide is effective, in terms of ameliorating hyperglycemia, as evidenced by an increase in beta-cell mass, after its administration, in partially pancreatectomized OLETF rats. Male rats, 6 weeks of age, were allocated at random to two groups, 70% pancreatectomy (Px) and sham-pancreatectomy (sham). The Px group was divided into three subgroups, based on treatment with either nicotinamide (350 mg/kg), phlorizin (400 mg/kg) or saline, which continued until 4 weeks after surgery, and were sacrificed at 4, 6, or 8 weeks after surgery. A 70% Px resulted in sustained hyperglycemia in the saline-treated Px rats, which was ameliorated by administration of either phlorizin or nicotinamide, showing the non-fasting blood glucose levels reached to or near the levels found in the sham rats. After cessation of phlorizin injection, non-fasting blood glucose level increased rapidly, reaching the level of the saline-treated Px rats at the end of the experiment, whereas after cessation of nicotinamide injection, non-fasting blood glucose increased gradually to a level which was significantly lower than that observed in the saline-treated Px rats. An increased beta-cell mass, 62.7 +/- 7.8% of total beta-cell mass induced by nicotinamide at 4 weeks, decreased gradually, reaching the level of pretreatment, 30.3 +/- 4.0% 4 weeks after cessation of the treatment. The findings in this study suggest that ameliorated hyperglycemia as a result of proliferated beta-cells during the administration of nicotinamide may results in showing beta-cell exhaustion (a majority of beta-cell degranulation) once stopping injection, as compared with phlorizin treated group in this model rat.
Department of Laboratory Medicine, University of Tokushima School of Medicine, Japan. shima@clin.med.tokushima-u.acjp
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Zhu
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Kuwajima
D000818:Animals; D001786:Blood Glucose / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D007328:Insulin / Q000032:analysis; D007515:Islets of Langerhans / Q000737:chemistry / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D009536:Niacinamide / Q000494:pharmacology*; D010180:Pancreatectomy; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D007328:Insulin; D009536:Niacinamide