Dimethylaminopurine inhibits metabolic effects of insulin in primary adipocytes.

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Dimethylaminopurine inhibits metabolic effects of insulin in primary adipocytes. / Göransson, Olga; Rydén, Mikael; Nilsson, Rebecka; Arner, Peter; Degerman, Eva.

I: Journal of Nutritional Biochemistry, Vol. 15, Nr. 5, 2004, s. 303-312.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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T1 - Dimethylaminopurine inhibits metabolic effects of insulin in primary adipocytes.

AU - Göransson, Olga

AU - Rydén, Mikael

AU - Nilsson, Rebecka

AU - Arner, Peter

AU - Degerman, Eva

PY - 2004

Y1 - 2004

N2 - Dimethylaminopurine (DMAP) has previously been used as an inhibitor of phosphorylation in studies of meiotic events, and more recently to investigate TNFα signaling, because of its potential to inhibit activation of c-jun N-terminal kinase (JNK). Here we have addressed the effects of DMAP on metabolic insulin responses in adipocytes and on intracellular insulin signaling molecules. At 100 μmol/L, DMAP completely inhibited the ability of insulin to counteract lipolysis in isolated adipocytes. Insulin-induced lipogenesis and glucose uptake was inhibited to a lesser degree in a concentration-dependent manner starting at 10 μmol/L DMAP. Insulin-induced tyrosine phosphorylation of the insulin receptor was not affected by DMAP. Insulin-induced activation of protein kinase B, a known mediator of insulin action, was not inhibited by 100 μmol/L, but to a low extent by 1 mmol/L DMAP in intact cells. This inhibition was not sufficient to affect activation of the downstream protein kinase B substrate phosphodiesterase 3B. The inhibition of activation of JNK as a possible mechanism whereby DMAP affects insulin-induced antilipolysis, lipogenesis, and glucose uptake, was investigated using the JNK inhibitor SP600125. At 100 μmol/L, SP600125 completely reversed the antilipolytic effect of insulin, as well as partially inhibited insulin-induced lipogenesis and glucose-uptake, indicating that JNK may be involved in mediating these actions of insulin. Inhibition of JNK by DMAP may therefore partly explain the negative impact of DMAP on insulin action in adipocytes.

AB - Dimethylaminopurine (DMAP) has previously been used as an inhibitor of phosphorylation in studies of meiotic events, and more recently to investigate TNFα signaling, because of its potential to inhibit activation of c-jun N-terminal kinase (JNK). Here we have addressed the effects of DMAP on metabolic insulin responses in adipocytes and on intracellular insulin signaling molecules. At 100 μmol/L, DMAP completely inhibited the ability of insulin to counteract lipolysis in isolated adipocytes. Insulin-induced lipogenesis and glucose uptake was inhibited to a lesser degree in a concentration-dependent manner starting at 10 μmol/L DMAP. Insulin-induced tyrosine phosphorylation of the insulin receptor was not affected by DMAP. Insulin-induced activation of protein kinase B, a known mediator of insulin action, was not inhibited by 100 μmol/L, but to a low extent by 1 mmol/L DMAP in intact cells. This inhibition was not sufficient to affect activation of the downstream protein kinase B substrate phosphodiesterase 3B. The inhibition of activation of JNK as a possible mechanism whereby DMAP affects insulin-induced antilipolysis, lipogenesis, and glucose uptake, was investigated using the JNK inhibitor SP600125. At 100 μmol/L, SP600125 completely reversed the antilipolytic effect of insulin, as well as partially inhibited insulin-induced lipogenesis and glucose-uptake, indicating that JNK may be involved in mediating these actions of insulin. Inhibition of JNK by DMAP may therefore partly explain the negative impact of DMAP on insulin action in adipocytes.

KW - Antilipolysis

KW - DMAP

KW - PKB

KW - JNK

KW - Insulin

KW - Adipocyte

U2 - 10.1016/j.jnutbio.2004.01.004

DO - 10.1016/j.jnutbio.2004.01.004

M3 - Article

VL - 15

SP - 303

EP - 312

JO - Nutrition Reports International

JF - Nutrition Reports International

SN - 1873-4847

IS - 5

ER -