Impaired Hormonal Regulation of Lipolysis and the Interference with Adenosine in Adipose Tissue from Hyperglycemic Sand Rats In Vitro

Summary

Sand rats (Psammomys obesus) developed in response to different food intake various states of hyperglycemia and hyperinsulinism. 12 normo- and 10 hyperglycemic animals were selected by means of a weekly control of plasma glucose and plasma insulin over a period of 12 weeks after separation from the mother. During this time also the development of body weight gain was checked. In both groups of rats the hormonal regulation of glycerol release by incubated adipose tissue was investigated.

In any case, the fat tissue from hyperglycemic sand rats showed a lower lipolytic responsiveness to noradrenaline stimulation than that of their normoglycemic controls. This correlates well with previous results in hyperglycemic sand rats in which the catecholamine-stimulated cAMP production was disturbed (Knospe and Köhler 1981).

Degradation of released adenosine by addition of adenosine deaminase significantly enhanced the noradrenaline action on glycerol release in both groups of sand rats. Even though the noradrenaline-stimulated lipolytic activity of adipose tissue from normo- and hyperglycemic animals was enhanced in the presence of adenosine deaminase, the hormone resistance of adipose tissue from hyperglycemic sand rats was nevertheless not abolished. The theophylline-mediated adenosine receptor blockade gave further evidence that particularly endogenous adenosine released during incubation of adipose tissue from sand rats inhibited the noradrenaline action on lipolysis. The antilipolytic action of insulin on glycerol release is negligibly low in normoglycemic as well as hyperglycemic sand rats.

The degradation of adenosine by adenosine deaminase failed to improve the insulin action. Adenosine addition completely blocked the stimulating effects of noradrenaline on glycerol release. By blocking the alpha adrenergic activity of noradrenaline with phentolamine it could be proved that the reduced hormonal responsiveness of fat tissue from hyperglycemic sand rats was not caused by an imbalance between alpha- and beta adrenergic receptors.

Our results confirm the assumption that in hyperglycemic sand rats the impaired hormonal regulation of cAMP release is reflected in a deranged lipolysis.

Key-Words:

Sand Rat - Hyperglycemia - Hyperinsulinism - Insulin Resistance - Catecholamine Resistance - Adipose Tissue - cAMP Release - Lipolysis - Adenosine - Theophylline Effect - Adrenergic Alpha Receptor Blockade