RENAL AND SPLANCHNIC EXCHANGE OF HUMAN BIOSYNTHETIC C-PEPTIDE IN TYPE-1 (INSULIN-DEPENDENT) DIABETES-MELLITUS

Biosynthetic human C-peptide or NaCl (154 mmol.l-1) was given intravenously to 13 Type 1 (insulin-dependent) diabetic patients to determine the renal and splanchnic exchange of C-peptide. Catheters were inserted percutaneously into an artery and a renal and hepatic vein. Infusions of C-peptide were given for 60 min at two dose levels (5 and 30 pmol . kg-1 . min-1). Insulin was infused throughout the study (0.5 mU . kg-1 . min-1) and plasma glucose was kept constant by a variable glucose infusion. The regional blood flows were measured by indicator dilution techniques. In 11 of the 13 patients basal C-peptide levels were not detectable. The arterial steady-state C-peptide concentration was 0.81 +/- 0.10 nmol-l-1 and 2.33 +/- 0.30 nmol-l-1 at the low and high rate infusions, respectively. Renal uptake was 124 +/- 18 pmol . min-1 at the low infusion corresponding to 39% of the infused amount. At the higher dose C-peptide infusion renal uptake increased to 155 +/- 21 pmol . min-1 (p < 0.05). Urinary excretion of C-peptide was 7 +/- 2 pmol . min-1 at the low dose infusion and increased to 34 +/- 6 pmol . min-1 at the high dose infusion (p < 0.01). The proportions of infused amount excreted were fairly constant and between 2% and 3%. No net exchange of C-peptide was found across the splanchnic vascular bed. The rate of glucose infusion had to be increased by 35% during the low dose C-peptide, but not during NaCl infusion in order to maintain a constant plasma glucose concentration. Arterial plasma concentrations of noradrenaline increased by 15-25% during both C-peptide and NaCl infusions. It is concluded that in patients with Type 1 diabetes (a) the kidney is the primary site of C-peptide removal, (b) renal metabolism rather than urinary excretion is the dominating process for C-peptide elimination (c) the excreted proportions of an infused amount of C-peptide were fairly constant between 2% and 3% and (d) no hepatic C-peptide catabolism could be detected.