C-peptide and Insulin in Liver Disease

Abstract

The liver is the primary organ of insulin clearance; thus, hyperinsulinism in peripheral blood may result from diminished insulin degradation rather than hypersecution. Proinsulin is cleaved in the pancreatic β-cell to insulin and C-peptide, which are released into the circulation in equimolar quantities. Unlike insulin, C-peptide is not degraded by liver, and in liver disease the peripheral C-peptide concentration is a better index of insulin secretion than is peripheral insulin concentration. Fasting plasma insulin concentration was raised in 21 cirrhotic patients (0.13 ± 0.02 vs. 0.06 ± 0.01 nmol per liter) despite normal fasting blood glucose concentrations. C-peptide concentrations and, therefore, insulin secretion did not differ from controls', and the C-peptide:insulin ratio was decreased in cirrhotic subjects (4.0 ± 0.5 vs 7.0 ± 1.1). After oral glucose, hyperinsulinemic cirrhotic subjects had similar C-peptide concentrations to those of cirrhotics with a normal insulin response in whom glucose values were similar. Hyperinsulinism (both fasting and after glucose) appears to result from diminished insulin degradation, therefore. To distinguish the roles of liver damage and of portal-systemic shunting, similar studies were performed in patients with ostensibly normal liver function but long-standing portal venous block. Despite mild hyperglycemia, hyperinsulinism was not found in these subjects, either fasting or after oral glucose. The fasting C-peptide:insulin ratio was normal, and only after stimulation of insulin secretion by glucose was a mild impairment of insulin degradation seen. The hyperinsulinism of hepatic cirrhosis is due to impaired insulin degradation; this is more likely to result from liver damage per se than from portal-systemic shunting.

Pancreatic expression of human insulin gene in transgenic mice.

“…It was not possible to measure the mouse C-peptide, but the relative level of expression of the human insulin gene can be indirectly estimated. The plasma human C-peptide concentration in transgenic mice is 5-20% of that found in humans (32), and the plasma insulin concentrations in transgenic mice are similar to those of control mice (our results) and of humans (34). All together, these facts suggest that the order of magnitude of the human insulin secretion in Tg74 mice is 10% of the total insulin secretion.…”

A New Form of Insulin Resistance with Growth Retardation, Fatty Liver, and Hypogonadotropic Hypogonadism

“…17). Some patients with liver disease may show impaired degradation of circulating insulin (17) or a decreased number of insulin receptors (I I) but these were not present in our patient. The fatty infiltration of his liver was most likely a result of abnormal glucose metabolism, as is seen in congenital lipodystrophy (28) and poorly controlled insulin-dependent diabetes mellitus (1 3), rather than the cause of his insulin resistance.…”

Influence of the metabolic sequelae of liver cirrhosis on nutritional intake

“…Earlier work linked hyperinsulinemia with deficient hepatic insulin extraction or the shunting of portal venous blood to the systemic circulation (31). There is, however, no consensus as to the exact mechanisms involved in the hyperinsulinemia of cirrhosis but portosystemic shunting seems unlikely because hyperinsulinemia is not found in patients with portal vein thrombosis and normal liver function (32). In the current study, there were no significant differences in insulin concentrations in patients with (n = 10) and without (n = 21) evidence of portosystemic shunting.…”