Interleukin-1–Receptor Antagonist in Type 2 Diabetes Mellitus

• Published in: The New England journal of medicine Vol. 356; no. 15; pp. 1517 - 1526
• Main Authors: Larsen, Claus M, Faulenbach, Mirjam, Vaag, Allan, Vølund, Aage, Ehses, Jan A, Seifert, Burkhardt, Mandrup-Poulsen, Thomas, Donath, Marc Y
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 12-04-2007
• Subjects: Apoptosis; Biological and medical sciences; Blood Glucose - metabolism; Body Mass Index; C-Reactive Protein - secretion; Clinical Medicine; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diabetes. Impaired glucose tolerance; Double-Blind Method; Endocrine pancreas. Apud cells (diseases); Endocrinology and Diabetes; Endocrinopathies; Endokrinologi och diabetes; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Gene Expression Regulation - drug effects; General aspects; Glucose Tolerance Test; Glucose Transporter Type 4 - genetics; Glucose Transporter Type 4 - metabolism; Glycated Hemoglobin A - metabolism; Heat-Shock Proteins - genetics; Heat-Shock Proteins - metabolism; Humans; Insulin Resistance - physiology; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - secretion; Interleukin 1 Receptor Antagonist Protein - adverse effects; Interleukin 1 Receptor Antagonist Protein - pharmacology; Interleukin 1 Receptor Antagonist Protein - therapeutic use; Interleukin-6 - blood; Klinisk medicin; Male; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Pancreas; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Receptors, Interleukin-1 - antagonists & inhibitors; Recombinant Proteins - pharmacology; Recombinant Proteins - therapeutic use; RNA, Messenger - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; Endocrinopathy; Type 2 diabetes; Medicine; Metabolic diseases; Interleukin 1 receptor antagonist
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa065213

The expression of interleukin-1–receptor antagonist is reduced in pancreatic islets in type 2 diabetes, and high glucose concentrations induce interleukin-1β production in human pancreatic beta cells, suggesting that the interleukin-1 pathway may be a treatment target. This randomized trial showed that the interleukin-1–receptor antagonist anakinra (100 mg) improved glycemia and beta-cell secretory function and reduced markers of systemic inflammation, as compared with placebo.
This randomized trial showed that the interleukin-1–receptor antagonist anakinra improved glycemia and beta-cell secretory function and reduced markers of systemic inflammation, as compared with placebo.
Type 2 diabetes mellitus occurs when beta-cell function fails to compensate for insulin resistance.
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,
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Beta-cell function progressively deteriorates with an increasing duration of diabetes,
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partly because of beta-cell demise through apoptosis.
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–
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Interleukin-1β, a proinflammatory cytokine
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implicated as an effector molecule of inflammatory beta-cell destruction leading to type 1 diabetes,
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inhibits the function and promotes the apoptosis of beta cells.
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Beta cells producing interleukin-1β have been observed in pancreatic sections obtained from patients with type 2 diabetes.
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Depending on culture conditions, high glucose levels increase beta-cell production and the release of interleukin-1β, followed by functional impairment and apoptosis.
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– . . .