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Insulin Action and Its Disturbances in Disease - part 4

Điều này có thể phản ánh suy giảm insulinmediated đàn áp của lipolysis trong các tế bào mỡ và ức chế suy giảm tiết glucagon từ các tế bào α-. Kể từ khi tăng nồng độ của FFA cho mỗi gia nhập đã được chứng minh để kích thích | 170 INSULIN RESISTANCE IN GLUCOSE DISPOSAL AND PRODUCTION IN MAN different approach Lewis et al.90 also found evidence of resistance to the direct suppressive effect of insulin on hepatic glucose production in T2D. In addition we found that suppression of both plasma FFA and glucagon levels were markedly impaired in T2D Figure 6.3 .41 This may reflect impaired insulin-mediated suppression of lipolysis in adipocytes and impaired suppression of glucagon secretion from the a-cells. Since elevated FFA levels per se have been shown to stimulate both glycogenolysis as well as gluconeogenesis 91 92 impaired insulin-mediated suppression of FFA may obviously influence hepatic insulin sensitivity. Similarly because hepatic glucagon sensitivity is normal in T2D 93 94 impaired insulin-mediated suppression of glucagon secretion may also influence hepatic insulin sensitivity.95 Using the tracer technique in combination with the 2H2O technique Gastaldelli et al. have quantitated gluconeogenesis in obesity and in T2D. In obese subjects the gluconeogenic rate was directly related to the degree of obesity 96 and in clamp studies of type 2 diabetic subjects gluconeogenic fluxes were elevated in the basal state and suppression in response to insulin was markedly impaired during the clamp.97 Thus from in vivo studies there is evidence of hepatic insulin resistance both in the direct and in the indirect actions through FFA and glucagon and both in the glycogenolytic and in the gluconeogenic pathways. Biochemical defects in hepatic insulin action Control of hepatic glucose output may occur through regulation of gluconeogenesis or glycogenolysis. However glucose-6-phosphatase G6Pase and glucokinase GK are believed to play prominent roles in the regulation of glucose production by controlling the rate of glucose efflux and uptake in hepatocytes. The competing activity between the two enzymes has been described as the glucose cycle and represents an important potential site of regulation.98