Beta-cell Diabetes Research Articles

Diabetic lymphocytes transfer and beta cell functions.

There is now consensus that the immune system is involved in the pathogenesis of insulin dependent diabetes mellitus (IDDM) in man and animals. This destructive autoimmune process may occur over a long-lasting period and only when a sufficient number of beta cells are destroyed does clinical evidence appear.

Abnormalities in glucose-stimulated insulin release, 45Ca uptake, and 86Rb efflux in diabetic Chinese hamster islets.

We loaded islets from normal and diabetic Chinese hamsters with 86Rb (an analogue for K+) and measured 86Rb efflux during stimulation with 20 mM D-glucose. Genetically diabetic Chinese hamsters were selected from a subline (L) known for subnormal pancreatic insulin release and excessive pancreatic glucagon release in vitro. 86Rb accumulation in 1 mM glucose was normal in the diabetic islets. Similar to the pattern of 86Rb efflux previously seen from normal rat and mouse islets, 20 mM glucose suppressed 86Rb efflux within 1-2 min, and efflux remained suppressed until return to 1 mM glucose in both normal and diabetic hamster islets. After the first 2 min of 20 mM glucose, suppression of 86Rb efflux was somewhat greater in the diabetic hamster islets than in the normals. In addition, glucose-stimulated insulin release and 45Ca uptake were significantly reduced in the diabetic islets. Therefore, in the diabetic hamster islets, there is at least no impairment in the initial suppression of 86Rb efflux by glucose. This suggests that the diabetic beta-cells recognize glucose and carry out the initial steps in the stimulus-secretion coupling sequence normally. The later, excessive suppression of 86Rb efflux may be due to impaired Ca2+-induced changes in 86Rb efflux, suggesting that defective regulation of intracellular Ca2+ activity, rather than defective regulation of K+ permeability, may lead to the impaired insulin secretion.

Venezuelan Encephalitis Virus–induced Alterations in Carbohydrate Metabolism in Genetically Diabetic Mice

We previously reported in this journal that the TC-83-vaccine strain of Venezuelan encephalitis (VE) virus results in a sustained diminution of glucose-stimulated insulin release in golden Syrian hamsters, persisting as long as 90 days after viral infection. This study was designed to examine the metabolic and pathologic consequences of TC-83 VE virus infection in C57 BL/Ks mice (+/+) and in genetic variants of this strain homozygous (db/db) and heterozygous (db/+) for the diabetic gene, db. Five-week-old mice of each genetic variant were inoculated subcutaneously, in groups of 18, with 100,000 plaque-forming units (PFU) of TC-83 that had not been passaged in chick embryo cells or with diluent (control mice). The clinical course in all three groups of mice following VE inoculation was mild, with a 5 to 10% mortality. By light microscopy, control +/+, TC-83 VE-infected +/+, control db/+, and TC-83 VE-infected db/+ pancreases manifested no appreciable difference in morphology. Uninfected db/db mice showed typical changes, including a definite decrease in the number of aldehyde fuchsin-staining granules in beta cells. TC-83 VE-infected db/db mice exhibited a profound decrease in pancreatic beta cell granulation on aldehyde fuchsin staining. After TC-83 VE inoculation, the most striking alterations in carbohydrate metabolism occurred in db/db mice, which showed further worsening of glucose tolerance 120 min after intraperitoneal glucose as well as significantly decreased basal and glucose-stimulated immunoreactive insulin (IRI) levels. After TC-83 VE infection, pancreatic IRI content was not decreased in +/+ or db/+ mice but was virtually absent in db/db mice. The data support the ability of TC-83 VE to inhibit glucose-stimulated IRI release in three genetic variants of C57 BL/Ks mice. In addition, this model demonstrates the heightened susceptibility of the remaining diabetic beta cells in the db/db mice to subsequent infection with a pancreatropic virus.

The Beta Cell in Diabetes—More Sinned Against than Sinning?

The Beta Cell in Diabetes—More Sinned Against than Sinning?

Beta-cell function improved by supplementing basal insulin secretion in mild diabetes.

Insulin supplements, predominantly as a constant basal fish insulin infusion, were given to patients with mild diabetes to reduce the overnight fasting glucose level to normal. The basal plasma human insulin levels were reduced to subnormal levels by the infusion, and the insulin response to intravenous glucose was enhanced. The beta-cell in diabetes seems to be in a vicious circle in which an impaired insulin response to glucose produces hyperglycaemia, which stresses beta-cell function, making it more inefficient. A constant basal insulin supplement to induce basal normoglycaemia may benefit beta-cell function in diabetes.