Peripheral insulin resistance precedes the onset of hyperglycemia in spontaneously diabetic Chinese hamsters of Asahikawa colony.

To investigate the pathogenesis of spontaneously diabetic Chinese hamsters 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 disposal in postabsorptive state using [3-3H]glucose. Glucose uptake of various tissues was assessed as glucose utilization index (R'g) by the 2-deoxyglucose method. Plasma insulin level was increased in prediabetic CHAD but not decreased in CHAD with short-term diabetes compared with control Chinese hamsters (non-diabetic strain). HGP of prediabetic CHAD was similar to that of control Chinese hamsters. However, after developing 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 inguinal, 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 difference of R'g in heart ventricle, diaphragm, tibialis anterior or brain was observed. In conclusion, insulin resistance in some muscles and brown and white adipose tissues precedes hyperglycemia and hepatic insulin resistance in CHAD. Hepatic overproduction of glucose (hepatic insulin resistance) is a major factor responsible for overt basal hyperglycemia and may play an important role in developing further diabetic state.