Growth hormone, insulin-like growth factor-1 and insulin resistance in cirrhosis

Abstract

Cirrhosis is characterized by paradoxical growth hormone secretion in response to glucose and insulin infusion. To ascertain whether this abnormality contributes to insulin resistance, euglycemic hyperinsulinemic glucose clamps were performed on six patients with cirrhosis and six normal control subjects. Each patient with cirrhosis underwent two clamps in random order, a clamp with somatostatin (250 micrograms/hr) together with insulin and glucagon replacement, and a control clamp without somatostatin. The normal subjects underwent the control clamp only. During the control clamp, growth hormone levels were considerably higher in the patients with cirrhosis (6.1 +/- 0.4 vs. 0.5 +/- 0.4 mU/L, p < 0.02), and glucose uptake was considerably lower (3.29 +/- 0.56 vs. 9.52 +/- 1.14 mg/kg/min, p < 0.001). Indirect calorimetry indicated that the defect was accounted for by lower nonoxidative glucose disposal (1.23 +/- 0.45 vs. 6.00 +/- 0.73, p < 0.001). Peripheral glucose uptake, exemplified by forearm glucose uptake (0.27 +/- 0.04 vs. 1.22 +/- 0.42 mg/100 ml/min, p < 0.02), and calculated insulin sensitivity (24 +/- 8 vs. 114 +/- 20 microliters/kg/min per mU/L) were particularly diminished. In the patients with cirrhosis somatostatin suppressed growth hormone levels (6.1 +/- 1.2 to 1.2 +/- 0.4 mU/L, p < 0.05). However, no significant changes occurred in whole-body glucose uptake (3.29 +/- 0.56 vs 3.01 +/- 0.54 mg/kg/min), forearm glucose uptake (0.27 +/- 0.04 vs 0.30 +/- 0.01 mg/100 ml/min) or insulin sensitivity (24 +/- 8 vs, 35 +/- 10 microliters/kg/min/mU/L, p = 0.42).(ABSTRACT TRUNCATED AT 250 WORDS)

Alterations in growth hormone receptor abundance regulate growth hormone signaling in murine obstructive cholestasis

“…Local GH-dependent and -independent synthesis of IGF-I in key target tissues, including skeletal muscle, likely also plays a key role in terms of regulating protein synthesis in an autocrine/ paracrine manner (18). Resistance to GH upregulation of liver IGF-I is seen in children and adults with obstructive cholestasis and cirrhosis and has been associated with decreased hepatic GHR and IGF-I expression (4,5,15,21,27,37). Physiological consequences of this phenomenon can include osteodystrophy, linear growth failure, and muscle catabolism (4,20).…”

A Survey of Correlation Between Insulin-Like Growth Factor-I (IGF-I) Levels and Severity of Liver Cirrhosis

“…Liver cirrhosis is a state accompanied by a decrease in IGF-1 and progression of the disease (9-13). In liver cirrhosis IGF-1 level would be decreased while growth hormone would be increased (14). This decrease in IGF-1 is because of two factors; firstly, the decrease in growth hormone receptors in patients with cirrhosis and secondly progressive reduction in production of IGF-1 that is due to a decrease in hepatocytes (15-17).…”

Expression of insulin-like growth factor-I and insulin-like growth factor binding proteins during thioacetamide-induced liver cirrhosis in rats

“…In patients with liver cirrhosis the IGF axis is severely disturbed, and these alterations are accompanied by reduced IGF-I [13][14][15][16], IGF-II [17] and IGFBP-3 serum concentrations [16,[18][19][20]. Low IGF-I levels are associated with adverse clinical outcome and frequent complications of advanced cirrhosis such as malnutrition [21,22], insulin resistance [23,24], impaired immunity [25], osteopenia [26,27], wasting of skeletal muscle [28], hypogonadism [29,30] and jejunal microvilli atrophy [31]. In line with these data recent in vivo studies have demonstrated that exogenous IGF-I improved liver function and reduced oxidative liver damage and fibrosis in experimental liver cirrhosis [32][33][34].…”