Insulin lipoprotein lipase stimulation

Progesterone has little effect on protein metabolism. It stimulates lipoprotein lipase activity and seems to favor fat deposition. The effects on carbohydrate metabolism are more marked. Progesterone increases basal insulin levels and the insulin response to glucose. There is... 

In human adipose tissue, palmitoyl-CoA is usually used in the first glycerol-3-phosphate acylation reaction. The next two acyl residues are normally unsaturated fatty acids oleic acid and, less commonly, linoleic acid. Triglyceride biosynthesis is stimulated by insulin, most likely via its activation of lipoprotein lipase and its activity in moving glucose into the cells. 

Insulin, among other things, also stimulates production of lipoprotein lipase (LPL). With insulin deficiency in diabetes, there is insufficient LPL to release fatty acids from the triglycerides of VLDL and chylomicrons (see Fig. 6.4), another reason for accumulating serum triglycerides, apart from increased VLDL production by the liver. 

The storage of triacylglycerols in adipose tissue is mediated by insulin, which stimulates adipose cells to secrete lipoprotein lipase and to take up glucose, the source of glycerol for triacylglycerol synthesis. 

C. VLDL levels are elevated because the decreased insulin and increased glucagon cause lipolysis of adipose triacylglycerols. The fatty acids and glycerol are repackaged in VLDL, which are secreted by the liver. Therefore, both triacylglycerols and cholesterol are elevated in the blood. Lipoprotein lipase is decreased because its synthesis and secretion by adipose tissue are stimulated by insulin. 

GIP stimulates insulin secretion only in the presence of mild to moderate hyperglycaemia (Andersen et al., 1978 Wahl et al., 1992), but not in the presence of normal glucose concentrations. In addition to secretion of insulin, GIP augments insulin-dependent inhibition of hepatic glycogenolysis (Elahi et al., 1986 Hartman et al., 1986). It also activates adipose tissue lipoprotein lipase (Eckel et al., 1978) and has been shown to stimulate fatty acid synthesis de novo in rat adipose tissue (Oben et al., 1991). 

Insulin causes activation of a protein tyrosine kinase in many cells. Insulin also causes increased glucose transport in selected tissues. Insulin will stimulate dephosphorylation of many proteins phosphorylated in response to cAMP. Insulin is an anabolic hormone and in many tissues causes increases in protein and glycogen synthesis. Insulin also causes an increase in adipose lipoprotein lipase and triacylglycerol storage in the adipose tissue. 

Fig. 33.24. Conversion of the fatty acid (FA) from the triacylglycerols (TG) of chylomicrons and VLDL to the TG stored in adipose cells. Note that insulin stimulates both the transport of glucose into adipose cells and the secretion of LPL from the cells. Glucose provides the glycerol 3-phosphate for TG synthesis. Insulin also stimulates the synthesis and secretion of lipoprotein lipase (LPL). Apoprotein C-II activates LPL.

Factors leading to characteristic dyslipidaemia are complex and not fully understood. Insulin resistance is associated with the failure of normal suppression of hormone-sensitive lipase in adipose tissue and increased lipolysis leading to increased flux of non-esterified fatty acids (NEFAs) to the liver this is partly responsible for increased hepatic output of very low-density lipoprotein (VLDL) [6]. Central obesity is common in insulin resistance and type 2 diabetes and visceral fat is increasingly recognised as an important paracrine and endocrine organ [7]. Adiponectin, an important adipose-specific adipokine, is reduced in insulin resistance and type 2 diabetes [8]. This would favour increased lipolysis as the action of a further important cytokine, TNF-alpha in stimulating lipolysis is unopposed. 

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