The kidney is responsible for a considerable part of the clearance of
insulin and
C-peptide. Two routes are thought to be involved in the renal extraction of
insulin and
C-peptide from the circulation: (1) glomerular filtration, and (2) uptake by tubular cells from peritubular capillaries. The aim of the present study was to investigate these processes in
non-insulin-dependent diabetes mellitus (
NIDDM). For this purpose we measured the renal extraction of
inulin,
insulin, and
C-peptide in 12
NIDDM patients and 16 control subjects during elective heart catheterization. In addition, a 24-h urine sample was obtained from all subjects to assess the fractional clearance of the
peptides. The total renal extraction of both
insulin and
C-peptide exceeded the amount that was extracted by filtration, confirming the supposition that both
peptides are cleared by an additional mechanism, most probably peritubular uptake. The peritubular uptake of
insulin in the
NIDDM group was not significantly different from that in the control subjects, whereas the
insulin extraction over the legs was significantly lower in
NIDDM than in the controls. The peritubular uptake of
C-peptide was significantly lower in
NIDDM, while the fractional clearance of
C-peptide was significantly higher. The latter indicates that the reabsorption of
C-peptide from the
luminal side of the tubular cell is impaired in
diabetes mellitus. It is therefore concluded that urinary
C-peptide excretion is not a reliable index for
insulin production in
NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS)