Hormonal control of lipolysis in perifused adipocytes from diabetic rats.
The responsiveness of adipocytes from diabetic rats to lipolytic and antilipolytic stimuli was examined in both an incubation system and a perifusion system. Lipolysis, measured by glycerol release, was initiated with varying concentrations of epinephrine or other agents. Incubated adipocytes prepared from streptozotocin-diabetic rats were more sensitive to low doses of epinephrine than controls, but at higher concentrations of hormone, glycerol release was greater from the control cells. However, maximal lipolytic responses to nonhormonal stimuli, forskolin and methylisobutylxanthine, were clearly greater in incubated adipocytes from diabetic animals. In vivo treatment of both control and diabetic animals with insulin decreased the responsiveness of perifused adipocytes to epinephrine in vitro, further demonstrating the importance of the in vivo hormone levels to lipolytic response of adipocytes. In vitro perifusion with insulin and epinephrine of cells from untreated diabetic animals demonstrated a reduced response to the acute administration of insulin. The interaction of insulin with diabetic adipocytes was further examined by incubating cells with [125I]iodoinsulin and examining the release of intact and degraded hormone during perifusion. The diabetic cells bound more labeled hormone than the control cells, but the release of intact hormone was similar in both types of cells. The diabetic cells, however, released more degraded hormone than did control cells. This suggests that the binding and degradation of insulin in diabetic cells is not impaired and that the decreased responsiveness of these cells to insulin is due to a postreceptor defect. Together these data show that decreased insulin in streptozotocin-diabetes results in increased sensitivity to lipolytic agents. In addition, the diabetes enhances the adipocyte's ability to remove insulin, i.e. increased binding and degradation. Thus, it is likely that the in vitro findings of up-regulation of receptors and increased degradation by the adipocytes are a true reflection of the in vivo insulin deficiency.
S S
SS
Solomon
C M
CM
Heckemeyer
J A
JA
Barker
W C
WC
Duckworth
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D008066:Lipolysis / Q000187:drug effects*; D010477:Perfusion; D051381:Rats; D013997:Time Factors
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D000241:Adenosine; D015056:1-Methyl-3-isobutylxanthine; D004837:Epinephrine