Genetics and diet as factors in development of diabetes mellitus

Cohen, Arthur; Teitelbaum, A.; Saliternik, R.

doi:10.1016/0026-0495(72)90046-7

Cited by 64 publications

(20 citation statements)

References 9 publications

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“…These animals develop hyperglycemia and glycosuria at the age of 1 month and have been shown to develop diabetic vascular complications. The downward-selected line are healthy rats, with no genetic predisposition to develop diabetes, that remain normoglycemic on a high-sucrose copper-poor diet (Cohen et al, 1972). Both study and control rats reach puberty after 45 to 75 days and have a lifespan of 2 to 3 years.…”

Section: Animalsmentioning

confidence: 99%

Osteoporosis in the Cohen Diabetic Rat: Correlation Between Histomorphometric Changes in Bone and Microangiopathy

Amir

Rosenmann

Sherman

et al. 2002

Laboratory Investigation

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SUMMARY:Osteoporosis is well documented in type I diabetes, but its occurrence is controversial in type II diabetes.Microangiopathy is a major complication of type I and type II diabetes. We studied bone and microvascular changes in the Cohen diabetic rat, a unique nonobese model of noninsulin-dependent diabetes mellitus. The aim of this study was to find whether there is a temporal correlation between the onset of these two complications. The diabetic rats were divided into three groups (A, B, and C) according to duration of diabetes (2 months, 3 months, and 7 to 8 months, respectively). Trabecular bone area was assessed by computerized image analysis and microangiopathy by means of renal function tests, histologic examination of the kidneys, and ultrastructural measurement of the width of capillary basement membranes. Bone density of the distal femur and vertebra was significantly reduced in the diabetic rats relative to the control rats in all three groups (Group A femur: 11.5 Ϯ 1.6% versus 21.8 Ϯ 3.0%, p Ͻ 0.02; Group A vertebra: 15.9 Ϯ 1.6% versus 28.5 Ϯ 2.0%, p Ͻ 0.02; Group C femur: 7.9 Ϯ 1.1% versus 29.6 Ϯ 3.5%, p Ͻ 0.001; Group C vertebra: 11.4 Ϯ 0.7% versus 37.1 Ϯ 1.9%, p Ͻ 0.002). Renal function tests were normal in the Group A diabetic rats and there was marked albuminuria in the Group C diabetic rats. Histologic changes in the kidneys were seen only in the Group C diabetic rats. Five of 15 Group C diabetic rats showed no albuminuria or histologic evidence of kidney damage. The bone density in this subgroup was reduced relative to controls to the same degree as that of the rats with renal damage. There was no evidence of capillary basement membrane thickening in the Group A diabetic rats. Our findings indicate that in the Cohen diabetic rat, osteoporosis precedes the onset of microangiopathy. Microangiopathy probably does not play an important role in the pathogenesis of osteoporosis in this animal model. (Lab Invest 2002, 82:1399 -1405.

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Section: Animalsmentioning

confidence: 99%

Osteoporosis in the Cohen Diabetic Rat: Correlation Between Histomorphometric Changes in Bone and Microangiopathy

Amir

Rosenmann

Sherman

et al. 2002

Laboratory Investigation

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“…he Cohen diabetic rat is an exceptional genetically derived experimental model of dietinduced type 2 diabetes that reproduces many features of the disease in humans (1)(2)(3)(4)(5). This rodent model stands out among other experimental models of type 2 diabetes in several important ways.…”

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confidence: 99%

“…This rodent model stands out among other experimental models of type 2 diabetes in several important ways. Its most outstanding and distinctive feature is that it expresses genetic susceptibility (sensitivity and resistance) to a carbohydrate-rich diet, a central feature of type 2 diabetes in humans (1,2,4,5) that is not present in other major genetically inbred rat strains that simulate type 2 diabetes in humans. The other major rat models of type 2 diabetes, the Goto-Kakizaki (GK) (6,7), the Otsuka Long-Evens Tokushima Fatty (OLETF) (8 -10), and the Zucker diabetic fatty (ZDF) rats (11,12) develop diabetes spontaneously, without any important relationship to the composition of diet.…”

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confidence: 99%

The Newly Inbred Cohen Diabetic Rat

et al. 2001

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The newly inbred Cohen diabetic rat is an exceptional experimental model of diet-induced type 2 diabetes mellitus that is the result of secondary inbreeding nearly 30 years after it originally had been established. Animals from the original colony were selectively inbred by stringent criteria for 10 additional generations, bringing overall inbreeding to >50 generations. The metabolic phenotypes of the resulting contrasting strains, designated as the Cohen diabetic-sensitive (CDs) and -resistant (CDr) rats, were characterized. The phenotype of the CDs strain that was fed a regular diet consisted of fasting normoglycemia, normal glucose tolerance to intraperitoneal glucose loading, normal fasting insulin levels, and a normal insulin response to glucose loading. In contrast, CDs rats that were fed a custom-prepared high-sucrose low-copper diabetogenic diet became overtly diabetic: fasting glucose levels were normal or elevated, and the blood glucose insulin response to glucose loading was markedly abnormal. CDr rats that were fed a regular or diabetogenic diet did not develop diabetes and maintained normal glucose tolerance and insulin secretion. A striking sex difference was observed in CDs rats that were fed a diabetogenic diet: males had a lower growth rate and a more severe glucose intolerance pattern than females. Gonadectomy shortly after weaning did not prevent the development of the diabetic phenotype in its early phase in either sex but markedly attenuated its expression in males at a later phase, abolishing the sex differences. Alternate-day feeding, as opposed to daily feeding, also attenuated the metabolic phenotype in males. The development of the diabetic phenotype in CDs rats that were fed a diabetogenic diet was not accompanied by obesity or hyperlipidemia. The genetic profile of the strains was established using 550 microsatellite markers evenly distributed throughout the rat genome. The rate of homozygosity within strain was >96%. The rate of polymorphism between the contrasting strains was 43%. We conclude that the metabolic phenotypes of the rebred colony of CDs and CDr rats and their genetic makeup render the Cohen diabetic rat a useful experimental model that is highly suitable for studying the interaction between nutritional-metabolic environmental factors and genetic susceptibility (sensitivity and resistance) for the development of type 2 diabetes. The model is also distinctively useful for investigating the effect of sex on the expression of the diabetic phenotype.

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“…The Cohen diabetic rat shares essential features with human non-insulin-dependent diabetes such as genetic and environmental disposition [9], an early phase of hyperinsulinaemia, and insulin resistance, followed by hypoinsulinaemia [10], a decreased number and sensitivity of insulin receptors…”

Section: Methodsmentioning

confidence: 99%

“…[Diabetologia (1995) 38: 899-905] [11], a metabolic response to hypoglydaemic drugs [12], and renal and retinal complications [13]. The procedure that leads to the development of diabetes in this model has been described in detail elsewhere [9]. Briefly, two lines of this strain were selected from parental "Sabra" rats (Hebrew University albino strain) by feeding a copper-deficient ( with spontaneous blood glucose levels over 16.6 mmol/1 were used in this study.…”

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confidence: 99%

Effect of myo-inositol supplementation on the development of renal pathological changes in the Cohen diabetic (type 2) rat

Cohen

Wald²,

Popovtzer³

et al. 1995

Diabetologia

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Summary A lower concentration of intracellular myo-inositol has been implicated in the development of diabetic nephropathy. This was based on short-term studies showing that early administration of aldose reductase inhibitors or myo-inositol supplementation reduces increased glomerular filtration rate and partly reduces increased urinary albumin excretion in streptozotocin diabetic rats. We studied the effect of long-term (4 months) administration of 1% myo-inositol supplement to the Cohen diabetic (type 2) rat on the development of nephropathy and renal Na+-K+-ATPase. This treatment reduced the increased renal Na+-K+-ATPase activity but had no effect on blood glucose levels, body weight, increased kidney weight, or creatinine clearance and did not prevent or reduce the development of renal glomerular pathology. There was no correlation between the level of Na+-K § ATPase activity and the degree of nephropathy. It is possible that the renal pathological changes are due to metabolic and humoral factors resulting from hyperglycaemia, other than myo-inositol depletion. The fact that rnyo-inositol treatment had no effect on the development of renal pathological changes but was shown to have a beneficial effect on restoring impaired conduction velocity and on the disruption of structural elements in the nerve indicates that the effect of the biological changes ensuing from hyperglycaemia vary in different tissues depending on local conditions. [Diabetologia (1995) 38: 899-905] Key words Non-insulin-dependent diabetes mellitus (type 2), myo-inositol, glomerulosclerosis, Na+-K +-ATPase, Cohen-diabetic rat.It has been suggested that polyol pathway hyperactivity contributes to the pathogenesis of diabetic renal complications [1][2][3][4]. This was based on the observation that treatment with aldose reductase inhibitors and myo-inositol supplements reduces the increased glomerular filtration rate [5,6] Abbreviations: Pi, Inorganic phosphate; IDDM, insulin-dependent diabetes mellitus; NIDDM, non-insulin-dependent diabetes mellitus; STZ-D, streptozotocin diabetic rats; GS, glomerulosclerosis; PG, prostaglandin.creased urinary albumin excretion [6][7][8] in diabetic animals.Most of these observations have been made in short-term type i streptozotocin diabetic rats (SZT-D). The purpose of the present study was to evaluate the effect of long-term supplementation of myo-inositol in the Cohen diabetic rat (type 2) on the development of pathological changes and Na+-K+-ATPase activity in the kidneys. Materials and methodsAnimals. The Cohen diabetic rat shares essential features with human non-insulin-dependent diabetes such as genetic and environmental disposition [9], an early phase of hyperinsulinaemia, and insulin resistance, followed by hypoinsulinaemia [10], a decreased number and sensitivity of insulin receptors

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Genetics and diet as factors in development of diabetes mellitus

Cited by 64 publications

References 9 publications

Osteoporosis in the Cohen Diabetic Rat: Correlation Between Histomorphometric Changes in Bone and Microangiopathy

Osteoporosis in the Cohen Diabetic Rat: Correlation Between Histomorphometric Changes in Bone and Microangiopathy

The Newly Inbred Cohen Diabetic Rat

Effect of myo-inositol supplementation on the development of renal pathological changes in the Cohen diabetic (type 2) rat

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