The functional significance of a spontaneous pancreatic islet change in aged rats

Hajdu, A.; Herr, Fiona; Róna, G

doi:10.1007/bf01241032

Cited by 14 publications

(6 citation statements)

References 8 publications

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“…Thus, a large number of the islets in these rats did not simply increase in volume, but also underwent major pathological changes ending in beta cell damage and fibrosis. The morphological findings of this study are similar to those described by Hadju and Rona (8,9) in a large survey of nonbreeder aging male rats, by Wexler and Fischer (3,4) in repeatedly bred male rats, and by Shino et al (10) in fatty Zucker rats. We suspect the common denominator here is not genetic makeup, breeding, or lack of same, but of obesity.…”

Section: Morphological Observationssupporting

confidence: 91%

Structure and function changes in the endocrine pancreas of aging rats with reference to the modulating effects of exercise and caloric restriction.

Reaven¹,

Reaven²

1981

J. Clin. Invest.

100

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A B S T R A C T The current study was conducted to determine if physical activity and/or weight control could influence the age-related decrease in beta cell insulin response noted in earlier studies. As such, virgin, male Sprague-Dawley rats were maintained in our facility for 1 yr on three differential experimental programs: in the first group, control rats lived under standard laboratory conditions; the second group ofrats ran several miles a day in exercise wheels; and the third group was given a calorie-restricted diet designed to keep the rats weight-matched with the exercising rats. The results showed that the 12-mo-old sedentary control rats weighed an average of 800 g. From the time these rats were 4 mo old, they were significantly hyperinsulinemic, with mean (±SEM) serum insulin levels of 55±6 ,uU/ml compared with their base-line levels at 1Y2 mo of 20±3,uU/ml. Morphological studies on the pancreas of these rats at the end of the year revealed enlarged, multilobulated, fibrotic islets. After collagenase digestion, the most normal-appearing islets from the 12-mo-old controls were used for insulin secretion studies, these islets showed significantly reduced glucose-induced insulin release (0.83 ,uU insulin/min per volume islet) compared with islets from young rats (1.80 ,uU insulin/min per volume islet). In contrast, 12-mo-old exercised or calorie-restricted rats weighed -500 g and did not show the changes in serum insulin levels or pancreas pathology exhibited by the sedentary control animals. However, islets from the calorie-restricted group functioned in vitro no better than islets from the sedentary control group. Islets from the exercised rats were somewhat improved in this regard. In summary, we believe exercise and weight control diminishes the animals' need for insulinresulting in youthful-appearing islets after a year's Receivedfor publication 8January 1981 and in revisedform 16 March 1981. time. However, these regimes do not appear able to correct the beta cell decline in function previously de-scribed.

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Section: Morphological Observationssupporting

confidence: 91%

Structure and function changes in the endocrine pancreas of aging rats with reference to the modulating effects of exercise and caloric restriction.

Reaven¹,

Reaven²

1981

J. Clin. Invest.

100

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“…Since there was no clear sex-difference in the incidence of pigmentation in the pancreatic islet, it is possible that micro-hemorrhage is common of SD rats and might even be a trigger for more overt hemorrhage. Generally, the incidence of spontaneous islet lesions including tumors has been reported to be more common in males than in females (Hajdu et al, 1968; Reaven et al, 1987; Ruhe et al, 1992, Dillberger; 1994; Majeed, 1997). Our results were also consistent with those in these previous investigations (Larsson et al, 1977; Nakama et al, 1985; Ahuja et al, 1987; Gomez Dumm et al, 1990; Mori et al, 1990; Dillberger 1994).…”

Section: Discussionmentioning

confidence: 99%

Age- and Sex-Related Differences in Spontaneous Hemorrhage and Fibrosis of the Pancreatic Islets in Sprague–Dawley Rats

2007

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To elucidate the spontaneous occurrence of hemorrhage in the pancreatic islet, naïve Crj:CD(SD)IGS rats were given a commercially available standard diet ad libitum over 20 weeks, and were sequentially examined. Islet hemorrhage was morphologically observed from 12 weeks of age, and its incidence was significantly higher in males than in females, with a wide distribution in all pancreatic lobes. The incidence (%) of affected islets to examined islets was increased with age. Hemorrhage was accompanied by brownish pigmentation, and reacted positively for iron by Prussian/Berlin blue staining. In 26 weeks old, most of the islets were dissected by dense fibrous tissue into small nests, and disarranged beta cells were detected by insulin immunostaining. Ultrastructurally, no apparent morphological change was seen in any islet endothelial cell, although blood leakage with migrated macrophages and dense collagen fibers was observed around the capillaries. In serum biochemistry of rats aged 26 weeks, the estradiol level in males with hemorrhage was significantly lower than that in males with non-hemorrhage, presumably suggesting the lack of capillary protective ability. Next, when rats were given a high fat/protein diet over 20 weeks to clarify whether it accelerated the frequency or timing of hemorrhage, its occurrence was essentially identical to that of the animals fed the standard diet. In conclusion, the onset of spontaneous islet hemorrhage was observed predominantly in aged males, resulting from the low estradiol level in serum.

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“…However, Hajdu and Rona detected islet changes only in males at least 40 wk (about 9.5 mo) old and did not find them in 20-wk-old rats. They suggested that the pathogenesis of the islet changes begins with an increased need for insulin, which causes compensatory @-cell hyperplasia and islet enlargement (9). With time, islet fibrosis occurs, dissecting islets into multiple discreet nodules of proliferating @ cells, a process they termed nodular regeneration.…”

Section: Islet Histopathologymentioning

confidence: 99%

Age-Related Pancreatic Islet Changes in Sprague-Dawley Rats

Dillberger¹

1994

Toxicol Pathol

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To characterize the clinical pathologic and morphologic features of spontaneous age-related changes in pancreatic islets observed in Crl:CDa(SD)BR rats, I reviewed data from rats used as controls in 10 toxicity studies from 1987 to 1992. Rats were 3.5-26 rno old at necropsy. At necropsy, rats were weighed, and serum, urine, and pancreas samples were collected. Serum was analyzed for glucose, triglyceride, and cholesterol concentrations; urine was analyzed for glucose and ketones; and samples of pancreas were stained with hematoxylin and eosin, Masson's trichrome stain, or for insulin by an immunoperoxidase method with a Masson's trichrome counterstain and examined microscopically. Male rats gained weight more rapidly than females and were visibly obese by 5 mo. Weight gain was accompanied by increased fasting triglyceride and cholesterol concentrations. Triglyceride increased more than cholesterol: from 3.5 to 17 rno ofage, triglyceride concentrations increased 3.4-fold in males and 3.1-fold in females. By 14 mo ofage, rats generally had fasting triglyceride concentrations >200 mg/dl (2.2 PM). Fasting glucose concentrations generally were slightly (<30%) greater in males than females. More males than females had glucose >200 mg/dl (1 1 mM); several males had glucose >300 mg/dl (16.5 mM). Glucosuria was not detected in any rat. Ketonuria was much more common in males than in females, but its incidence did not parallel that of obesity and hypertriglyceridemia; instead, ketonuria was most common in young males and decreased with age. Morphologic islet changes were observed in rats as young as 3.5 mo old, and their incidence increased with age. They were much more common in males than in females at all ages. Islet changes began as @-cell hyperplasia causing enlarged islets. With time, fibrosis gradually dissected islets into discreet nests of cells separated by bands of collagenous tissue so that they resembled cirrhotic liver. As the process continued, the ratio of fibrous tissue to islet cells increased until some islets were reduced to scattered @ cells imbedded in a mass of scar tissue. By the time rats were 26 mo old, enlarged islets were rare; instead, remaining islets generally were small. Islet cell neoplasia did not occur in rats 17 mo of age or younger. In 26-mo-old rats, neoplasms were more common in males than in females (incidence of 20% vs lo%, respectively). The pathogenesis of these abnormalities is unclear, but they suggest that male Sprague-Dawley rats fed ad libitum are a less than ideal system in which to conduct long-term toxicity/safety assessment studies or any other research studies that could be influenced by altered metabolism. These results also reveal that male and female Sprague-Dawley rats differ metabolically and that the differences may predispose males to islet cell neoplasms.

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The functional significance of a spontaneous pancreatic islet change in aged rats

Cited by 14 publications

References 8 publications

Structure and function changes in the endocrine pancreas of aging rats with reference to the modulating effects of exercise and caloric restriction.

Structure and function changes in the endocrine pancreas of aging rats with reference to the modulating effects of exercise and caloric restriction.

Age- and Sex-Related Differences in Spontaneous Hemorrhage and Fibrosis of the Pancreatic Islets in Sprague–Dawley Rats

Age-Related Pancreatic Islet Changes in Sprague-Dawley Rats

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