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Am J Physiol Regul Integr Comp Physiol 265: R577-R583, 1993;
0363-6119/93 $5.00
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AJP - Regulatory, Integrative and Comparative Physiology, Vol 265, Issue 3 577-R583, Copyright © 1993 by American Physiological Society


ARTICLES

Norepinephrine- and insulin-resistant glucose transport in brown adipocytes from diabetic SHR/N-cp rats

A. Marette, P. Mauriege, J. P. Despres, O. L. Tulp and L. J. Bukowiecki
Department of Physiology, Faculty of Medicine, Laval University, Quebec, Canada.

The effects of norepinephrine and insulin on glucose transport were investigated 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) controls to test whether the decreased calorigenic response to norepinephrine of O-SHR adipocytes was specifically associated with alterations in glucose metabolism. Norepinephrine and insulin independently stimulated glucose transport in L-LA, O-LA, and L-SHR brown adipocytes, but 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. The number of high-affinity beta 1/beta 2-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 present 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 defects are predominantly involved in O-SHR adipocyte refractoriness to norepinephrine, and 3) a reduced mitochondrial content may represent the principal metabolic alteration explaining the decreased effects of norepinephrine on both thermogenesis and glucose transport. It is postulated that the marked insulin resistance of O-SHR leads to a decreased mitochondriogenesis in BAT, resulting in a diminished tissue thermogenic capacity and reduced glucose metabolism, thereby contributing to obesity and diabetes.


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X. Liu, F. Perusse, and L. J. Bukowiecki
Mechanisms of the antidiabetic effects of the beta 3-adrenergic agonist CL-316243 in obese Zucker-ZDF rats
Am J Physiol Regulatory Integrative Comp Physiol, May 1, 1998; 274(5): R1212 - R1219.
[Abstract] [Full Text] [PDF]




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