title: Antidiabetic Effect of Interleukin-1β Antibody Therapy Through β-Cell Protection in the Cohen Diabetes-Sensitive Rat.
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.
authors.affiliation: Diabetes Unit, Department of Internal Medicine and Hadassah Diabetes Center, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Genya
authors.initials: G
authors.lastname: Aharon-Hananel
authors.affiliation: Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany Centre of Anatomy, Hannover Medical School, Hannover, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Jörns
authors.affiliation: Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany.
authors.forename: Sigurd
authors.initials: S
authors.lastname: Lenzen
authors.affiliation: Diabetes Unit, Department of Internal Medicine and Hadassah Diabetes Center, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Itamar
authors.initials: I
authors.lastname: Raz
authors.affiliation: Diabetes Unit, Department of Internal Medicine and Hadassah Diabetes Center, Hadassah-Hebrew University Medical Center, Jerusalem, Israel sarahz@hadassah.org.il.
authors.forename: Sarah
authors.initials: S
authors.lastname: Weksler-Zangen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D003920:Diabetes Mellitus / Q000517:prevention & control*; D004040:Dietary Carbohydrates / Q000633:toxicity; D005951:Glucose Tolerance Test; D050417:Insulin-Secreting Cells / Q000502:physiology*; D053583:Interleukin-1beta / Q000276:immunology*; D009929:Organ Size; D010179:Pancreas / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D013395:Sucrose / Q000008:administration & dosage / Q000633:toxicity
chemical_list: D000911:Antibodies, Monoclonal; D004040:Dietary Carbohydrates; D053583:Interleukin-1beta; D013395:Sucrose