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Antidiabetic Effect of Interleukin-1β Antibody Therapy Through β-Cell Protection in the Cohen Diabetes-Sensitive Rat
- Source :
- Diabetes. 64:1780-1785
- Publication Year :
- 2014
- Publisher :
- American Diabetes Association, 2014.
-
Abstract
- Interleukin (IL)-1β, the sole proinflammatory cytokine released from pancreas-infiltrating macrophages, inhibits glucose-stimulated insulin secretion (GSIS), causing hyperglycemia in Cohen diabetes-sensitive (CDs) rats fed a diabetogenic-diet (CDs-HSD). Because IL-1β blockade is a potential therapeutic target in diabetes, we examined whether treating CDs rats with IL-1β antibody (IL-1βAb; 0.5 mg/kg body weight) could counteract the inhibition of GSIS and hyperglycemia. We found that daily IL-1βAb injections had a beneficial effect on glucose tolerance and insulin secretion in CDs-HSD rats. In the oral glucose tolerance test, IL-1βAb–treated CDs-HSD rats showed lower blood glucose concentrations (P < 0.001) and higher GSIS (P < 0.05) compared with nontreated CDs-HSD rats. IL-1βAb treatment also protected the exocrine pancreas; the number of infiltrating macrophages decreased by 70% (P < 0.01) and IL-1β expression decreased by 85% (P < 0.01). In parallel, a 50% reduction (P < 0.01) in the rate of apoptosis and in fat infiltration (P < 0.05) was noted in the exocrine parenchyma of IL-1βAb–treated CDs-HSD rats compared with nontreated CDs-HSD rats. Altogether, these data demonstrate that blocking IL-1β action by IL-1βAb counteracted β-cell dysfunction and glucose intolerance, supporting the notion that prevention of pancreas infiltration by macrophages producing IL-1β is of crucial importance for the preservation of β-cell function and prevention of diabetes.
- Subjects :
- Sucrose
endocrine system
medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
Interleukin-1beta
Cell
Proinflammatory cytokine
Insulin-Secreting Cells
Internal medicine
Diabetes mellitus
Diabetes Mellitus
Dietary Carbohydrates
Internal Medicine
medicine
Animals
Insulin secretion
Pancreas
business.industry
Antibodies, Monoclonal
Rats, Inbred Strains
Organ Size
Glucose Tolerance Test
medicine.disease
Rats
Blockade
Interleukin 1β
medicine.anatomical_structure
Endocrinology
Antibody therapy
business
Subjects
Details
- ISSN :
- 1939327X and 00121797
- Volume :
- 64
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....e3449edb18bda7771e1261e3119fc886
- Full Text :
- https://doi.org/10.2337/db14-1018