Metabolism of C-peptide in the dog. In vivo demonstration of the absence of hepatic extraction.

Abstract

A B S T R A C T The in vivo hepatic metabolism of connecting peptide (C-peptide) in relation to that of insulin has not been adequately characterized. A radioimmunoassay for dog C-peptide was therefore developed and its metabolism studied in conscious mongrel dogs, with sampling catheters chronically implanted in their portal and hepatic veins and femoral artery. The hepatic extraction of endogenous C-peptide under basal conditions was negligible (4.3±4.5%) and was similar to the hepatic extraction of C-peptide measured during the constant exogenous infusion of C-peptide isolated from dog pancreas. Simultaneously measured hepatic extraction of endogenous and exogenously infused insulin were 43.8±7.6 and 47.5±4.4%, respectively. The metabolic clearance rate of infused C-peptide was 11.5±0.8 ml/kg per min and was constant over the concentration range usually encountered under physiological conditions. In additional experiments, the effect of parenteral glucose administration on the hepatic extraction of C-peptide and insulin was investigated. The hepatic extraction of C-peptide (6.2±4.0%) was again negligible in comparison with that of insulin (46.7±3.4%). Parenteral glucose administration did not affect the hepatic extraction of either peptide irrespective of whether it was infused peripherally, intraportally, or together with an intraportal infusion of gastrointestinal inhibitory polypeptide. The fasting C-peptide insulin molar ratio in both the portal vein (1.2±0.1) and femoral

Restored insulin inhibition on insulin secretion in nondiabetic severely obese patients after weight loss induced by bariatric surgery

“…C-peptide was chosen to evaluate insulin secretion because of their equivalent molar ratio secretion, negligible hepatic extraction 25 and similar clearance in lean and obese subjects. 8 Regardless of the method used for calculation, insulin secretion was much higher in the obese in the first study, and the decrease after weight loss was important and statistically significant even in the second study, with further reduction in the third study.…”

Lack of insulin inhibition on insulin secretion in non-diabetic morbidly obese patients

“…Insulin secretion during a fasting and during insulin infusion in the euglycemic clamp was assessed using the Cpeptide plasma levels and, during the OGTT, the posthepatic insulin delivery rate was calculated from the insulin clearance and the insulin area. C-peptide was chosen to evaluate insulin secretion because of their equivalent molar ratio secretion, the negligible hepatic extraction 32 and similar clearance in lean and obese subjects. 9 Regardless of the method used for calculation, insulin secretion was about three times higher in obese patients compared to lean subjects.…”

The in vivo regulation of pulsatile insulin secretion

“…Insulin and C-peptide are co-released in a 1 to 1 molar ratio [77]. Whereas insulin undergoes substantial (40±80 %) and variable [66, 78±80] hepatic-insulin extraction [81], C-peptide is presumably not cleared by the liver [82], which resulted in a predominance of the use of C-peptide when calculating the overall insulin secretory rates. C-peptide kinetics are similar under different conditions and thus suited for a comparison of insulin release among different groups [83].…”