Peripheral neuropathy in mouse hereditary diabetes mellitus

Abstract

C57BL/KsJ db/db inbred mice have an hereditary autosomal recessive disease resembling in some respects maturity onset human diabetes mellitus. At 8--11 months of age, they displayed intermittent symptoms suggestive of a mild sensory neuropathy. These symptoms consisted of adduction of their hind limbs and flexing hind paws when raised by the tail, and inability to maintain their position on the roto wheel. Peripheral nerves and sensory ganglia of the diabetic mice were compared with those of the unafflicted littermates and studied with respect to Schwann cell counts and myelinated nerve fiber diameter measurements. In addition, teased fibers of peripheral nerves were compared for obvious changes in internodal distance and demyelination. Chromatolytic neurons were moe abundant in lumbosacral spinal ganglia of diabetic mice than in corresponding ganglia of controls or in more anterior spinal ganglia and trigeminal ganglia of diabetics. Histologic studies showed an increase in Schwann cell counts in longitudinal sections of peripheral nerves. A similar but larger increase was observed in peripheral nerves of mice affected with an hereditary sensory neuropathy, dystonia musculorum. A small but general decrease in myelinated fiber diameter was observed in sensory and motor nerves.

Functional Aspects and Pathogenetic Considerations of the Neuropathy in the Spontaneously Diabetic Bb‐wistar Rat

“…Animals with advanced diabetes also exhibited microangiopathic changes characterized by basement membrane thickening. This sequence of structural changes is similar to those reported in other spontaneously diabetic laboratory animals (Sima & Robertson, 1978a;Hanker et al, 1980;Yagihasi et al, 1981), and has led to the opinion that diabetic neuropathy is basically an axonal disorder (Jacobsen, 1976a;197613;Y agihashi et al, 1978;Sima & Robertson, 1979;Robertson & Sima, 1980;Sima, 1980aSima, , 1980bBrown et al, 1980). However, our knowledge concerning factors responsible for the development of nerve dysfunction in diabetes is scanty.…”

Ultrastructural and metabolic changes associated with reproductive tract atrophy and adiposity in diabetic female mice

“…Alterations in pancreatic (Coleman, 19781, renal (Like et al, 1972), CNS (Garris et al, 1985a,b), peripheral nerve (Hanker et al, 1980), and hepatic (Coleman, 1982) structure and function are recognized to occur in association with the diabetes syndrome in this murine model. The changes are influenced by the duration of the hyperglycemic-hyperinsulinemic condition that characterizes the expression of the genetic mutation in this murine model.…”

Effects of estradiol and progesterone on diabetes‐associated utero‐ovarian atrophy in C57BL/KsJ (db/db) mutant mice

“…Although the present studies focused on the intracellular structural and functional parameters modified by the diabetes-obesity syndrome in (dbldb) mice, similar cellular changes may relate to alterations in pancreatic, renal, hepatic and CNS tissue function in this model (Barlett and Garris, 1987;Bower et al, 1980;Bray and York, 1979;Coleman, 1967Coleman, ,1978Coleman, ,1982Garris, 1984aGarris, , 1987aGarris et al, 1984aGarris et al, ,b, 1985aGarris and Michel, 1988;Gartner, 1979;Hanker et al, 1980;Herberg and Coleman, 1977;Johnson and Sidman, 1979;Like et al, 1974;Meade et al, 1981;Moore et al, 1980;Sima and Robertson, 1979). Regardless of the particular tissue, the longer the diabetic condition persists, the more pronounced and dramatic are the cellular alterations in this animal model.…”

“…Alterations in follicular growth and recruitment patterns, ovarian steroid production, corpus luteum formation, cellular and interstitial structure, uterine epithelial activity, endometrial sensitivity to exogenous steroid therapy, and ovarian refractoriness to pituitary gonadotrophin stimulation are well-recognized consequences of the diabetes-obesity syndrome in this mutant mouse model (Barlett and Garris, 1987;Coleman, 1967;Garris, 1985Garris, , 1987bJohnson and Sidman, 1979;Garris et al, 1984aGarris et al, ,b, 1985aGarris et al, -c, 1986. In addition, the accompanying changes in pancreatic, hepatic, renal, neuronal, and peripheral nerve structure and function are associated with the expression of the altered carbohydrate metabolism and imbalanced glucose homeostasis, characterized by overt hyperglycemia and hyperinsulinemia [Bower et al, 1980;Bray and York, 1979;Coleman, 1967Coleman, , 1978Coleman, , 1982Garris et al, 1985a-c, Gartner, 1979Hanker et al, 1980;Like et al, 1974;Meade et al, 1981;Moore et al, 1980;Sima and Robertson, 1979). Changes in cellular glucose uptake rates (Garris et al, 1984a(Garris et al, ,b, 1985aGarris and Michel, 1988), as well as noradrenergic counterregulatory influences (Garris, 1988b1, exacerbate the diabetes-associated depression in intercellular processing, responsivity , sensitivity, structure, and function (Garris, 1985;Garris et al, 1985aGarris et al, -q 1986.…”