Suppression of Beta-Cell Secretion by Somatostatin Does Not Fully Reverse the Disproportionate Proinsulinemia of Type 2 Diabetes

  1. Michael E. Røder12 and
  2. Steven E. Kahn1
  1. 1Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle, Washington
  2. 2Clinic of Internal Medicine, Endocrine Section, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
  1. Address correspondence and reprint requests to Michael E. Røder, MD, DMSc, Clinic of Internal Medicine I, Endocrine Section, Bispebjerg Hospital, University of Copenhagen, Bispebjerg Bakke 23, DK-2400 Copenhagen NV, Denmark. E-mail: mir{at}


Disproportionate hyperproinsulinemia is a feature of β-cell dysfunction in type 2 diabetes. It has been hypothesized that this abnormality represents an intrinsic abnormality of the β-cell and/or may result from an increase in β-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 β-cell secretory demand. An arginine stimulation test was performed before and at the end of the clamp to measure β-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 β-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 β-cell function exists in subjects with type 2 diabetes that may be aggravated by increased secretory demand.


  • This article is based on a presentation at a symposium. The symposium and the publication of this article were made possible by an unrestricted educational grant from Servier.

    • Accepted June 1, 2004.
    • Received March 12, 2004.
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