Simulated Hyperglycemic Hyperosmolar Syndrome: <i>IMPAIRED INSULIN AND EPINEPHRINE EFFECTS UPON LIPOLYSIS IN THE ISOLATED RAT FAT CELL</i>

B. Paul Turpin; William C. Duckworth; Solomon S. Solomon

doi:10.1172/JCI109316

Simulated Hyperglycemic Hyperosmolar Syndrome: IMPAIRED INSULIN AND EPINEPHRINE EFFECTS UPON LIPOLYSIS IN THE ISOLATED RAT FAT CELL

B. Paul Turpin, William C. Duckworth, and Solomon S. Solomon

Published March 1, 1979 - More info

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Abstract

These investigations were designed to evaluate the effect of excess glucose and sodium chloride on lipolysis in the isolated adipocyte under normal and modelled pathological conditions simulating the hyperglycemic hyperosmolar syndrome.

Isolated rat fat cells were incubated in the presence of various combinations of sodium chloride, glucose, epinephrine, and insulin. Lipolysis was measured as glycerol and free fatty acid release, and total medium osmolarity as milliosmoles per liter by freezing point depression.

Basal lipolysis was unaffected by changes in osmolarity with sodium chloride, but glucose and glucose plus sodium chloride increased basal glycerol release. Increasing osmolarity with sodium chloride diminished the lipolytic response to epinephrine. Increasing osmolarity with glucose augmented the lipolytic response to epinephrine up to a total medium osmolarity of 550 mosmol. Higher osmolarities produced with glucose suppressed the epinephrine-induced lipolytic response.

When the hyperglycemic hyperosmolar syndrome was simulated with 100 mM glucose and 50 mM sodium chloride (total osmolarity = 460 mosmol) the epinephrine-stimulated lipolysis dose-response curve in the isolated fat cell was shifted to the right. Furthermore, in the presence of 100 mM glucose + 50 mM sodium chloride, physiological concentrations of insulin were less effective in opposing epinephrine-stimulated lipolysis. In the presence of 50 mM glucose and 25 mM sodium chloride (total osmolarity = 370 mosmol) epinephrine-stimulated lipolysis measured as free fatty acid release was decreased by 50%.

Under conditions simulating the hyperglycemic hyperosmolar syndrome in the isolated rat adipocyte, altered lipolysis reflects impaired effectiveness of both insulin and epinephrine as antilipolytic and lipolytic hormones, respectively. Furthermore, the attenuated response to both hormones appears to be primarily a function of extracellular solute composition. The lack of ketosis is the result of diminished release of free fatty acids from peripheral adipose cells.