Genetically Determined Response to Different Ingested Carbohydrates in the Production of Diabetes

Am, Cohen

doi:10.1055/s-0028-1093449

Cited by 15 publications

(9 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Diabetes in this model has many features in common with human, non-insulin dependent diabetes (21). The rats were genetically selected from the Hebrew University albino rat strain for their genetic propensity to develop impaired carbohydrate metabolism when fed a copper-poor high-sucrose diet.…”

Section: Methodsmentioning

confidence: 99%

Effects of Nisoldipine on Hypertension and Glomerulosclerosis in Cohen Diabetic Rat with Goldblatt Hypertension

Rosenthal

Rosenmann²,

Cohen³

1993

Clinical and Experimental Hypertension

View full text Add to dashboard Cite

Nisoldipine treatment for five months prevented a rise in blood pressure in Cohen diabetic rats with Goldblatt hypertension, compared to a significant elevation in untreated controls. Blood creatinine and urea also decreased significantly in the treated animals, and renal lesions were less severe. The prevalence of glomerulosclerosis, however, remained unaltered in both the treated and control groups. These findings indicate that increased blood pressure aggravates renal changes, while reducing it eliminates the aggravation.

show abstract

Section: Methodsmentioning

confidence: 99%

Effects of Nisoldipine on Hypertension and Glomerulosclerosis in Cohen Diabetic Rat with Goldblatt Hypertension

Rosenthal

Rosenmann²,

Cohen³

1993

Clinical and Experimental Hypertension

View full text Add to dashboard Cite

show abstract

“…Prolonged administration of either a high fructose or sucrose diet to genetically selected rats induces a metabolic syndrome characterised by insulin resistance and decreased glucose tolerance, as well as increased plasma triglyceride and cholesterol levels (Cohen et al 1977, Cohen 1978. We have previously reported that administration of a sucrose-rich diet (SRD) to normal rats for 6 months induced such metabolic abnormalities, together with a significant increase in both pancreatic islet number and -cell area (Lombardo et al 1996).…”

Section: Introductionmentioning

confidence: 99%

Mechanisms involved in the beta-cell mass increase induced by chronic sucrose feeding to normal rats

Zotto¹,

Dumm²,

Drago³

et al. 2002

Journal of Endocrinology

View full text Add to dashboard Cite

The aim of the present study was to clarify the mechanisms by which a sucrose-rich diet (SRD) produces an increase in the pancreatic -cell mass in the rat. Normal Wistar rats were fed for 30 weeks either an SRD (SRD rats; 63% wt/wt), or the same diet but with starch instead of sucrose in the same proportion (CD rats). We studied body weight, serum glucose and triacylglycerol levels, endocrine tissue and -cell mass, -cell replication rate (proliferating cell nuclear antigen; PCNA), islet neogenesis (cytokeratin immunostaining) and -cell apoptosis (propidium iodide). Body weight (g) recorded in the SRD rats was significantly (P<0·05) larger than that of the CD group (556·0 8·3 vs 470·0 13·1). Both serum glucose and triacylglycerol levels (mmol/l) were also significantly higher (P<0·05) in SRD than in CD rats (serum glucose, 8·11 0·14 vs 6·62 0·17; triacylglycerol, 1·57 0·18 vs 0·47 0·04). The number of pancreatic islets per unit area increased significantly (P<0·05) in SRD rats (3·29 0·1 vs 2·01 0·2). A significant increment (2·6 times) in the mass of endocrine tissue was detected in SRD animals, mainly due to an increase in the -cell mass (P=0·0025). The islet cell replication rate, measured as the percentage of PCNA-labelled cells increased 6·8 times in SRD rats (P<0·03). The number of apoptotic cells in the endocrine pancreas decreased significantly (three times) in the SRD animals (P=0·03). The cytokeratin-positive area did not show significant differences between CD and SRD rats. The increase of -cell mass induced by SRD was accomplished by an enhanced replication of cells together with a decrease in the rate of -cell apoptosis, without any evident participation of islet neogenesis. This pancreatic reaction was unable to maintain serum glucose levels of these rats at the level measured in CD animals.

show abstract

“…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.…”

mentioning

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.…”

mentioning

confidence: 99%

The Newly Inbred Cohen Diabetic Rat

et al. 2001

View full text Add to dashboard Cite

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.

show abstract

Genetically Determined Response to Different Ingested Carbohydrates in the Production of Diabetes

Cited by 15 publications

References 8 publications

Effects of Nisoldipine on Hypertension and Glomerulosclerosis in Cohen Diabetic Rat with Goldblatt Hypertension

Effects of Nisoldipine on Hypertension and Glomerulosclerosis in Cohen Diabetic Rat with Goldblatt Hypertension

Mechanisms involved in the beta-cell mass increase induced by chronic sucrose feeding to normal rats

The Newly Inbred Cohen Diabetic Rat

Contact Info

Product

Resources

About