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The influence of insulin on adipose tissue differentiation, metabolism and adipokine secretion
Insulin is a key regulator of glucose homeostasis and stimulates glucose transport into fat cells by translocation of glucose transporters from inside the cell to the cell surface. Insulin stimulates lipid accretion in a dose dependent manner during preadipocyte differentiation in adipose tissue -derived stromal-vascular (SV) cell cultures used to study porcine preadipocyte differentiation. During differentiation CCAAT/enhancing binding protein (C/EBP) α expression confers the development of insulin-sensitive glucose transport in preadipocytes. In S-V cell culture studies crosstalk between C/EBPα and insulin–stimulated phosphatidylinositol 3–kinase (PI3K)/protein kinase B (Akt) pathways were involved in Akt2 and sirtuin-1 regulation of preadipocyte adipogenesis. In other SV studies insulin induced hypertrophy of porcine preadipocytes was accompanied by increases in fatty acid synthesis (FAS) activity and sterol regulatory element binding transcription factor-1 gene expression. Other evaluations of insulin responsiveness in SV cell culture studies will also be reviewed. Metabolism studies of adipose tissue from growing and market weight pigs have produced very inconsistent responses to insulin. For instance, studies of isolated adipocytes from 55 kg or 80 kg pigs demonstrated insulin stimulated lipogenesis and FAS activity in a dose-dependent manner in subcutaneous (SQ) and perirenal depots. In contrast, studies of adipose tissue slices from 20-60 kg pigs showed little to no effects of insulin on lipogenesis. In older pigs (80 to 127 kg), a 50% stimulation of lipogenesis by insulin was demonstrated. A study of isolated adipocytes from market weight pigs demonstrated that neutralization of endogenous adenosine and pertussistoxin-sensitive G-protein Gi decreased basal rates of lipogenesis and increased the insulin response to 160% above basal. Evidence of multiple intracellular signal pathways for insulin influence on adipose tissue will be reviewed. An exaggerated rate of glucose metabolism in basal conditions may contribute to inconsistent insulin responses of pig adipose tissue lipogenesis. Studies of intracellular signal pathways involved in insulin inhibition of lipolysis will also be reviewed. A number of adipokines are expressed by porcine adipose tissue including adiponectin and leptin but studies of adipokine and insulin interaction are few. One interaction included leptin reduction of insulin-mediated inhibition of lipolysis in porcine SV cultures. Insulin has a major role in porcine adipose tissue metabolism and development.
Keywords: insulin, porcine adipose tissue, metabolism, development.