Possible Role of α-Cell Insulin Resistance in Exaggerated Glucagon Responses to Arginine in Type 2 Diabetes
- Naomi Tsuchiyama, MD,
- Toshinari Takamura, MD, PHD,
- Hitoshi Ando, MD, PHD,
- Masaru Sakurai, MD,
- Akiko Shimizu, MD,
- Ken-ichiro Kato, MD,
- Seiichiro Kurita, MD, PHD and
- Shuichi Kaneko, MD, PHD
- From the Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
- Address correspondence and reprint requests to Toshinari Takamura, Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8641, Japan. E-mail: ttakamura{at}m-kanazawa.jp
Abstract
OBJECTIVE—Inappropriate excessive secretion of glucagon, which contributes to postprandial hyperglycemia, is a novel target for the treatment of diabetes. In this study, we sought to determine the factors associated with exaggerated glucagon secretion in response to an arginine challenge in patients with type 1 and type 2 diabetes.
RESEARCH DESIGN AND METHODS—Changes in circulating C-peptide immunoreactivity (CPR) and immunoreactive glucagon (IRG) after an arginine challenge were investigated in 35 patients with type 1 diabetes, 130 patients with type 2 diabetes, and 35 nondiabetic control subjects.
RESULTS—No significant differences were found in the basal level and the area under the concentration-time curve (AUC) of IRG (AUCIRG) among type 1 and type 2 diabetic patients and nondiabetic subjects. However, there was an inverse correlation between the AUCIRG and the AUC of CPR (AUCCPR) for type 1 (r = −0.388, P = 0.023) and type 2 (r = 0.396, P < 0.0001) diabetic patients, whereas AUCIRG was not correlated with AUCCPR in nondiabetic subjects (r = −0.079, P = 0.655). In type 1 diabetic patients, the AUCCPR decreased and the AUCIRG increased with increasing disease duration. In type 2 diabetic patients, both AUCIRG and AUCCPR increased with increasing BMI, basal CPR level, and homeostasis model assessment of insulin resistance value.
CONCLUSIONS—Our findings suggest that the pathophysiology of the exaggerated glucagon response differs between type 1 and type 2 diabetes. Intraislet insulin deficiency and α-cell insulin resistance may be the primary contributors to this condition in type 1 and type 2 diabetes, respectively.
- AUC, area under the concentration-time curve
- CPR, C-peptide immunoreactivity
- HOMA-IR, homeostasis model assessment of insulin resistance
- IRG, immunoreactive glucagon
- QUICKI, quantitative insulin sensitivity index
Footnotes
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Published ahead of print at http://care.diabetesjournals.org on 31 July 2007. DOI: 10.2337/dc07-0066.
Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/dc07-0066.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted July 13, 2007.
- Received January 11, 2007.
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