Norepinephrine- and insulin-resistant glucose transport in brown adipocytes from diabetic SHR/N-cp rats.
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.
Marette
A
A
Department of Physiology, Faculty of Medicine, Laval University, Quebéc, Canada.
Mauriège
P
P
Després
J P
JP
Tulp
O L
OL
Bukowiecki
L J
LJ
D002001:Adipose Tissue, Brown / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000473:pathology; D004351:Drug Resistance; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006824:Hybridization, Genetic; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D007333:Insulin Resistance; D009638:Norepinephrine / Q000494:pharmacology*; D009765:Obesity / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D011412:Propanolamines / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011922:Rats, Mutant Strains
D007328:Insulin; D011412:Propanolamines; D005947:Glucose; C033394:CGP 12177; D009638:Norepinephrine