Suppression of Beta-cell secretion by somatostatin does not fully reverse the disproportionate proinsulinemia of type 2 diabetes

Diabetes. 2004 Dec;53 Suppl 3:S22-5. doi: 10.2337/diabetes.53.suppl_3.s22.


Disproportionate hyperproinsulinemia is a feature of beta-cell dysfunction in type 2 diabetes. It has been hypothesized that this abnormality represents an intrinsic abnormality of the beta-cell and/or may result from an increase in beta-cell secretory demand. To address this, six patients with type 2 diabetes and six age- and BMI-matched normal subjects received a combined 3-h insulin and somatostatin clamp to decrease beta-cell secretory demand. An arginine stimulation test was performed before and at the end of the clamp to measure beta-cell peptide release. In keeping with the reduction in secretory demand, C-peptide levels were suppressed by 60-80% during the clamp, as were proinsulin (PI) levels. The arginine-stimulated PI/C-peptide ratio decreased in the diabetic subjects from 4.4 +/- 1.5% before to 1.8 +/- 0.5% after the clamp (P < 0.01). This latter ratio was similar to that observed in the normal subjects before the somatostatin infusion (1.5 +/- 0.3%). In the normal subjects, after the clamp the PI/C-peptide ratio had decreased to 0.8 +/- 0.3% (P <0.01). Thus, the postclamp PI/C-peptide ratio in the subjects with type 2 diabetes was elevated compared with that in the normal subjects (P <0.05). Based on these observations, while relief of secretory demand on beta-cells by somatostatin decreases the disproportionate elevation in PI levels in patients with type 2 diabetes, the failure to normalize this measure suggests that an intrinsic abnormality of beta-cell function exists in subjects with type 2 diabetes that may be aggravated by increased secretory demand.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Female
  • Humans
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Male
  • Middle Aged
  • Proinsulin / blood*
  • Reference Values
  • Somatostatin / pharmacology*


  • Blood Glucose
  • Somatostatin
  • Proinsulin