NOREPINEPHRINE-RESISTANT AND INSULIN-RESISTANT GLUCOSE-TRANSPORT IN BROWN ADIPOCYTES FROM DIABETIC SHR N-CP RATS/

The effects of norepinephrine and insulin on glucose transport were in vestigated in brown adipocytes isolated from obese nondiabetic Lister and Albany (LA/N-cp strain) rats (O-LA), obese diabetic spontaneously hypertensive (SHR/N-cp strain) rats (O-SHR), and from their lean (L) c ontrols to test whether the decreased calorigenic response to norepine phrine of O-SHR adipocytes was specifically associated with alteration s in glucose metabolism. Norepinephrine and insulin independently stim ulated glucose transport in L-LA, O-LA, and L-SHR brown adipocytes, bu t their stimulatory effects were markedly reduced in O-SHR cells. Both insulin responsiveness and the total number of insulin receptors were significantly decreased in O-SHR adipocytes but not in O-LA cells. Th e number of high-affinity beta1/beta2-adrenoceptors was significantly increased (+70%) in O-LA adipocytes but was similar in L-SHR and O-SHR cells. These results indicate that 1) major metabolic defects are pre sent in brown adipose tissue (BAT) of O-SHR but not of O-LA, although these two strains are homozygous for the cp allele, 2) postreceptor de fects are predominantly involved in O-SHR adipocyte refractoriness to norepinephrine, and 3) a reduced mitochondrial content may represent t he principal metabolic alteration explaining the decreased effects of norepinephrine on both thermogenesis and glucose transport. It is post ulated that the marked insulin resistance of O-SHR leads to a decrease d mitochondriogenesis in BAT, resulting in a diminished tissue thermog enic capacity and reduced glucose metabolism, thereby contributing to obesity and diabetes.