Lin_2000_Dig.Dis.Sci_45_1517

We investigated possible impairment of the signal transduction system in gastric myocytes of streptozotocin-induced diabetic (STZ) and spontaneous diabetic WBN/Kob (WBN/Kob) rats. Gastric motility 10 weeks after the onset of diabetes mellitus was significantly reduced in both diabetic rats compared with control, and the decreased motility was not recovered by the administration of insulin to maintain normal blood glucose levels. There was no significant difference between both types of diabetic rats and control rats in total number of [3H]quinuclidinyl benzilate ([3H]QNB) binding sites (Bmmax: 545-587 fmol/mg protein) on gastric smooth muscle cell membranes or in the affinity of [3H]QNB for the binding sites (Kd: 0.06-0.07 nM). Immunoblot analysis using polyclonal anti-G-protein antibodies indicated increased expression of Gsalpha in gastric smooth muscle cell membranes, but no significant change in Gialpha or Gq/11alpha expression in STZ rats, and decreased expression of Gq/11alpha with no significant change in Gsalpha and Gialpha in WBN/Kob rats. The cAMP production in gastric smooth muscle cell membranes was augmented in the absence and presence of 100 microM isoproterenol, and 100 microM forskolin in STZ rats, whereas no significant change of cAMP production was observed in WBN/Kob rats irrespective of the presence of the stimulants. These findings suggest that long-standing diabetes may induce alterations in signal transduction at downstream receptors in gastric myocytes, resulting in the impairment of gastric motility, although the mechanism of reduced contractile activity may differ between STZ and WBN/Kob rats.