title: Cytokine sensitivity of Langerhans' islets of diabetes-prone BB/OK rats under hypoglycemic conditions.
abstract: Islets of Langerhans isolated from diabetes-prone BB/OK rats were exposed to interleukin-1beta (IL-1beta) or to a combination of tumor necrosis factor-alpha (TNF-alpha) plus interferon-gamma (IFN-gamma) under hypoglycemia at glucose concentrations of 2.2 and 3.2 mmol/l or in the presence of stimulatory conditions at 6.0 and 11 mmol/l glucose. For estimating cytokine effects the islets were functionally assayed by measurement of glucose stimulated insulin secretion. Pancreatic islets exposed for 24 h to IL-1beta at a glucose concentration of 6.0 mmol/l exhibited a reduced insulin secretion following a 48h recovery period compared to islets which were cytokine treated at 2.2 or 3.2mmol/l glucose, respectively. Islets pre-exposed for 24h to TNF-alpha plus IFN-gamma at 2.2, 3.2 or 6.0 mmol/l glucose displayed no alterations of insulin secretion following a 48 h regeneration. A temporary (3 h) influence of IL-1beta under hyperglycemic conditions at 11 mmol/l glucose caused a reduction of the subsequent insulin secretion of Langerhans' islets prior incubated for 24 h at 6.0 mmol/l glucose without cytokines, but not of islets precultured at 2.2 mmol/l glucose. In contrast, a 3 h treatment with TNF-alpha plus IFN-gamma at 11 mmol/l glucose did not affect insulin secretion of islets prior held at 6.0 mmol/l glucose, whereas a transient exposure for 6h to IL-1beta as well as TNF-alpha plus IFN-gamma under similar conditions diminished insulin secretion of islets preincubated at 2.2 or 6.0 mmol/l glucose. In conclusion, hypoglycemia reduces the sensitivity of BB/OK rat islets to IL-1beta, whereas a slight elevation of glucose concentration to 6.0 mmol/l increases again their vulnerability. TNF-alpha plus IFN-gamma at concentrations capable to decrease insulin secretion of islets during hyperglycemia do not affect the insulin output in a range between 2.2 and 6.0 mmol/l glucose. During glucose stimulation at 11 mmol/l islets' insulin secretory machinery is protected from IL-1beta as well as TNF-alpha plus IFN-gamma for 3 h by a preceding 24 h hypoglycemia, but its vulnerability is restored within additional 3 h.
authors.affiliation: Institute of Pathophysiology, D-1 7495 Karlsburg, Ernst-Moritz-Arndt-University of Greifswald, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Schröder
authors.forename: Gerhild
authors.initials: G
authors.lastname: Wachlin
authors.forename: Ingrid
authors.initials: I
authors.lastname: Klöting
authors.forename: Siegfried
authors.initials: S
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism; D005947:Glucose / Q000276:immunology / Q000378:metabolism; D007003:Hypoglycemia / Q000276:immunology* / Q000378:metabolism; D007328:Insulin / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D007375:Interleukin-1 / Q000276:immunology* / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D011913:Rats, Inbred BB; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism
chemical_list: D007328:Insulin; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D005947:Glucose