Effect of early dietary restriction on insulin action and secretion in theGK rat, a spontaneous model of NIDDM

The availability of the Goto-Kakisaki (GK) rat model of non-insulin-depende nt diabetes mellitus prompted us to test the effect of a limited period of undernutrition in previously diabetic young rats on their insulin secretion and insulin action during adult age. Four-week-old female GK rats were eit her food restricted (35% restriction, 15% protein diet) or protein and ener gy restricted (35% restriction, 5% protein diet) for 4 wk. Food restriction in the young GK rat lowered weight gain but did not aggravate basal hyperg lycemia or glucose intolerance, despite a decrease in basal plasma insulin level. Furthermore, the insulin-mediated glucose uptake by peripheral tissu es in the GK rat was clearly improved. We also found that food restriction, when it is coupled to overt protein deficiency in the young GK rat, altere d weight gain more severely and slightly decreased basal hyperglycemia but conversely aggravated glucose tolerance. Improvement of basal hyperglycemia was related to repression of basal hepatic glucose hyperproduction, despit e profound attenuation of basal plasma insulin level. Deterioration of tole rance to glucose was related to severe blunting of the residual glucose-ind uced insulin secretion. It is, however, likely that the important enhanceme nt of the insulin-mediated glucose uptake helped to limit the deterioration of glucose tolerance.