Naslov
Reversal of hyperglycemia-induced insulin resistance on amino acid transport in cultured rat hepatocytes

Autori
Roša, Jagoda ; Roša Josip

Izvornik
Periodicum biologorum (1849-0964) 101 (1999), 1; 1-6

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

Ključne riječi
AIB-transport; hepatocytes; hyperglycemia; insulin resistance

Sažetak
Background and purpose: Hyperglycemia appears to be a significant etiologic factor in the development of insulin resitance in NIDDM and in poorly controlled IDDM. Yet, the cellular events that lead to resistance to insulin action following hyperglycemiaare not well understood. The objective of this investigation was to determine whether and how high glucose may directly cause damage to cellular function and insulin action in liver cells. The effects of a high glucose concnentration and the possible role of protein kinase C (PKC) activity in the development of insulin resistance were investigated in cultured rat hepatocytes isolated from normal rats. Material and methods: Hepatocytes were isolated by a modified collagenase perfusion tecgnique of Berry nad Friend from normal rats and were cultured for 24 and 72 h in the medium containing either low (5 mmol/l) or high (25 mmol/l) glucose without (basal) or with (0,08 umol/l) insulin. For study AIB transport hepatocytes were incubated in Hanks-Hepes medium containing 2 g/l albumin and alfa-amino isobutyric acid in the absance (basal) and presence of 0,08 ľmol/l insulin for one hour. PKC stimulator (TPA) and inhibitor polimixin B were added to the medium during transport assay. The cells were digested in 0,2 N NaOH and an aliquot was taken for the determination of protein and radioactivity in a liquid scintillation counter. Results: High glucose reduced basl and insulin-stimulated AIB transport in hepatocytes isolated from normal rats after 24 hj and led to more than 100% reductions in insulin action after 72 hour. Furthermore, normalization of basal transport and insulin action following 24 h exposure to the normoglycemia has been demonstrated. Following short-term (1h) treatment with protein kinase C (PKC) inhibitor polimyxin B, the impaired capacity for basal and insulin-stimulated AIB transport was normalized aftere 5 h normoglycemia. Conclusions: These data suggest that chronic elevation of glucose has deleterious effect on basal AIB transport and contributes to the insulin resistance, and that this process is likely to be modulated by changes in PKC activity. The main conclusion from our study is that the defects occurred over a relatively short period of time and were reversible.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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