PERIPHERAL INSULIN-RESISTANCE PRECEDES THE ONSET OF HYPERGLYCEMIA IN SPONTANEOUSLY DIABETIC CHINESE-HAMSTERS OF ASAHIKAWA COLONY

To investigate the pathogenesis of spontaneously diabetic Chinese hams ters of Asahikawa colony (CHAD), hepatic glucose production (HGP) and glucose uptake of several tissues were determined before the onset of hyperglycemia (prediabetic state). HGP was calculated as glucose dispo sal in postabsorptive state using [3-H-3]glucose. Glucose uptake of va rious tissues was assessed as glucose utilization index (R'g) by the 2 -deoxyglucose method. Plasma insulin level was increased in prediabeti c CHAD but not decreased in CHAD with short-term diabetes compared wit h control Chinese hamsters (non-diabetic strain). HGP of prediabetic C HAD was similar to that of control Chinese hamsters. However, after de veloping overt hyperglycemia (> 200 mg/100 ml), HGP increased linearly with plasma glucose level. R'g of adductor longus, extensor digitorum longus and triceps was significantly decreased in prediabetic CHAD. R 'g of interscapular brown adipose tissue, white adipose tissue from in guinal, dorsal and epididymal sites were also decreased in prediabetic CHAD. Thus, peripheral insulin resistance precedes the development of hyperglycemia and may be a primary defect in CHAD. No significant dif ference of R'g in heart ventricle, diaphragm, tibialis anterior or bra in was observed. In conclusion, insulin resistance in some muscles and brown and white adipose tissues precedes hyperglycemia and hepatic in sulin resistance in CHAD. Hepatic overproduction of glucose (hepatic i nsulin resistance) is a major factor responsible for overt basal hyper glycemia and may play an important role in developing further diabetic state.