Naslov
Dexamethasone reverses insulin resistance induced by hyperglycemia in cultured hepatocytes isolated from normal rats

Autori
Roša, Jagoda ; Roša, Josip

Izvornik
Diabetologia Croatica (0351-0042) 26 (1997), 4; 199-207

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
insulin; dexamethasone; glycogen; hepatocytes; hyperglycemia
(insulin; dexamethasone;glycogen; hepatocytes; hyperglycemia;)

Sažetak
This study was undertaken to determine the specific effect of hyperglycemia on the decrease of liver glycogen in diabetes, and the contribution of hyperglycemia to insulin resistance. Normal rat hepatocytes were cultured in a serum-free medium containing a high glucose concentration (27,8 mmol/l) with or without insulin (0.08 umol/l) and with or without dexamethasone. (1 umol/l) or with both hormones for 24, 48 and 72 h. The initial glycogen content was 1.05+-0.13 umol/mg protein. Twenty-four- hour hyperglycemia did not affect the ability of cells to accumulate glycogen in response to glucose and a continuous glycogen deposition of up to 1.86 +- 0.17 umol/mg protein was recorded. There was no significant difference between insulin-stimulated and glucose-induced deposition of glycogen.On the other hand, basal D-U14Cglucose incorporationwas 12.18+-0.73 umol/mg protein/h, accompanied by an increased glucose turnover, since the insulin-stimulated incorporation was significantly higher (21.63+-3 umol/mg protein). Seventy-two-hour hyperglycemia led to a 3-fold reduction of basal D-U14C glukose incorporation into glycogen (3.99+-0.3 umol/mg protein/h) and to glycogen mobilisation, whereby the content of glycogen was degraded to a very low level (0.2+-0.07 umol/mg protein. Insulin was not able to suppress glycogenolysis and increase basal D-U14C glucose incorporation into glycogen. Dexamethasone preserved the effect of insulin. After 72-h hyperglycemia, the insulin -stimulated D-U14C glucose incorporation was 57.94+-5 umol/mg protein/h. Furthermore, with dexamethasone insulin was able to continuously stimulate glycogen synthesis, so that on day 3 glycogen concentration was 3.75+-0.33 umol/mg protein. In conclusion, long-term hyperglycemia (72 h) led to a significant decrease in glucose effectiveness on hepatic glycogen sinthesis and could induce insulin resistance. Dexamethasone opposed this glucotoxic effect of hyperglycemia on insulin action and normalisation of insulin-stimulated glycogen deposition and D-U14C glucose incorporation into glicogen was observed in vitro, however, there was no in vitro reversal in the ability of glucose itself to promote the synthesis of glycogen.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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