Recent developments in metabolism that impinge on research into the nature and treatment of diabetes mellitus.
It has been established that adenosine, its agonists, or antagonists can cause dramatic changes in insulin sensitivity in isolated soleus muscle and, moreover, can modify changes in sensitivity caused by pathophysiological conditions. Addition of adenosine deaminase to the incubation medium, which is known to lower the concentration of adenosine, increases the sensitivity of glycolysis to insulin. Addition of an adenosine-receptor agonist decreases sensitivity by about 10-fold, whereas addition of an adenosine-receptor antagonist increases sensitivity by about 10-fold. The latter totally removes the resistance of glucose utilization to insulin in the isolated soleus muscle obtained from either the genetically obese rat or from the rat fed a high sucrose diet. These findings strongly support the view that changes in insulin sensitivity in muscle can be brought about either by acute changes in the local concentration of adenosine or in the affinity or number of receptors for adenosine in muscle. However, in many of the conditions investigated, in which insulin sensitivity in muscle is changed, there was no correlation between the change in the adenosine content of the muscle and altered insulin sensitivity. It has also been shown that prostaglandin E1 can increase dramatically the sensitivity of glycolysis to insulin and that this is a specific effect of prostaglandins of the E series. It is not produced by prostacyclins, thromboxanes, or leukotrienes. It is unclear if there is a relationship between the effects of adenosine and prostaglandins. Chronic elevation of catecholamines may increase the sensitivity of glucose utilization to insulin and also increase the rate of thermogenesis by substrate cycling.(ABSTRACT TRUNCATED AT 250 WORDS)
Newsholme
E A
EA
Department of Biochemistry, University of Oxford, United Kingdom.
D000241:Adenosine / Q000378:metabolism; D001833:Body Temperature Regulation; D002395:Catecholamines / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy*; D015444:Exercise; D005973:Glutamine / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D007333:Insulin Resistance; D011453:Prostaglandins / Q000378:metabolism
D002395:Catecholamines; D007328:Insulin; D011453:Prostaglandins; D005973:Glutamine; D000241:Adenosine