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

Am J Physiol. 1993 Sep;265(3 Pt 2):R577-83. doi: 10.1152/ajpregu.1993.265.3.R577.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Brown / metabolism*
  • Adipose Tissue, Brown / pathology
  • Animals
  • Biological Transport / drug effects
  • Diabetes Mellitus / metabolism*
  • Diabetes Mellitus / pathology
  • Drug Resistance
  • Female
  • Glucose / metabolism*
  • Hybridization, Genetic
  • Insulin / metabolism
  • Insulin / pharmacology*
  • Insulin Resistance
  • Norepinephrine / pharmacology*
  • Obesity / metabolism*
  • Oxygen Consumption / drug effects
  • Propanolamines / metabolism
  • Rats
  • Rats, Inbred SHR
  • Rats, Mutant Strains

Substances

  • Insulin
  • Propanolamines
  • Glucose
  • CGP 12177
  • Norepinephrine