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-1β (IL-1β) or to a combination of tumor necrosis factor-α (TNF-α) plus interferon-γ (IFN-γ) 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-1β at a glucose concentration of 6.0 mmol/l exhibited a reduced insulin secretion following a 48 h recovery period compared to islets which were cytokine treated at 2.2 or 3.2 mmol/l glucose, respectively. Islets pre-exposed for 24 h to TNF-α plus IFN-γ 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-1β 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-α plus IFN-γ 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 6 h to IL-1β as well as TNF-α plus IFN-γ 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-1β, whereas a slight elevation of glucose concentration to 6.0 mmol/l increases again their vulnerability. TNF-α plus IFN-γ 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-1β as well as TNF-α plus IFN-γ for 3 h by a preceding 24 h hypoglycemia, but its vulnerability is restored within additional 3 h.

• Diabetes-prone BB rat
• Langerhans' islets
• Cytokines
• Insulin secretion
• Islet vulnerability