A Study of Glucose Tolerance and Insulin Response in Partially Depancreatized Dogs

Sun, Anthony M.; Coddling, Judith A.; Haist, R. E.

doi:10.2337/diab.23.5.424

Cited by 42 publications

(20 citation statements)

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“…This probably reflects the islet cell mass which has successfully implanted. This apparent failure of insulin secretion appears similar to the "exhaustion" seen clinically after subtotal pancreatectomy [7], and experimentally in partially pancreatectomized animals [8], although the exact cause remains unknown. One possible cause may be that a reduced mass of B cells may be able to maintain fasting normoglycaemia, but at other times, when hyperglycaemia ensues, the chronic secretory overstimulation resulting from persistent hyperglycaemia results in eventual exhaustion.…”

Section: Discussionmentioning

confidence: 82%

The effect of hyperglycaemia on pancreatic islets transplanted into rats beneath the kidney capsule

et al. 1989

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Summary. The effect of hyperglycaemia on islet transplantation in the rat has been examined in two ways, using syngeneic transplantation of 400 islets to the kidney capsule and subsequent measurement of kidney insulin content as a measurement of B-cell survival. Firstly, islets were transplanted into either diabetic or normal rats, then 6 months later the composite kidney/islet graft was transplanted into a normal rat. The insulin content was measured after a further 6 months and was found to be significantly reduced in islets exposed to hyperglycaemia in the primary recipient. These findings are interpreted as showing that long-term exposure of islets to hyperglycaemia results in B-cell loss. In the second experiment 400 islets were transplanted into either a long-term (6 months) diabetic or a normal rat. Two weeks later the composite kidney/islet graft was transplanted into a normal rat. The insulin content was measured after a further 6 months and no significant difference was found, whether the primary recipient was diabetic or not. These results are interpreted as showing that islet graft implantation is not impaired in longterm diabetic rats.Key words: Hyperglycaemia, islet transplantation, diabetes, rat.Persistent hyperglycaemia has long been suspected of having a detrimental effect on pancreatic islet function [11. The influence of persistent hyperglycaemia on pancreatic islet transplantation has not been investigated in detail, although it could be deleterious in at least two ways. The first is a direct effect on the transplanted islets themselves which could be important after transplantation. The second is the effect of long-term hyperglycaemia on the recipient which might impair successful implantation of the transplanted islets.We have developed a quantitative model of islet transplantation in the rat [2] and have used an adaptation of this model to investigate both of the above possibilities in the rodent. By transplantation of a mass of islets insufficient to reverse diabetes we have previously shown that short-term exposure of islets to hyperglycaemia did not result in impaired implantation or loss of tissue mass [21. However, the possibility remains that long-term exposure to hyperglycaemia results in exhaustion with eventual loss of the transplanted insulin secreting tissue and this possibility was in no way excluded by our previous study [2]. We have also adapted this model to determine whether the implantation of islets was impaired in animals exposed to hyperglycaemia for prolonged periods prior to transplantation. Materials and methods Animals and induction of diabetesDark Agouti (DA) rats (bred in the Biomedical Services Unit, John Radcliffe Hospital) were used as both donors and recipients. One sibling of paired littermate DA rats was made diabetic by i.v. injection of streptozotocin 65 mg/kg, diabetes being confirmed by a repeated serum glucose of > 22 mmol/1 2 weeks later, Isolation of pancreatic isletsPancreatic islets were isolated from 3 donors by an intraductal collagenase technique...

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Section: Discussionmentioning

confidence: 82%

The effect of hyperglycaemia on pancreatic islets transplanted into rats beneath the kidney capsule

et al. 1989

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“…* p < 0.001 between group 2 and isolated islets and group 1. ** p < 0.001 between isolated islets and groups 3 and 4 beta-cell mass than restoring it [24], and under several clinical and experimental conditions normoglycaemia has been maintained with just 10-30 % of the normal islet tissue [25][26][27]. In insulin-treated mice, transplanted islets had to maintain, but not restore, normoglycaemia.…”

Section: Discussionmentioning

confidence: 97%

Improved outcome of islet transplantation in insulin-treated diabetic mice: effects on beta-cell mass and function

et al. 1997

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“…These results correspond with previous findings on the transplantation therapy of the pancreas in humans and the experimental pancreatectomy in animals; the donors of 50 to 80% extirpated pancreas can keep the normal PG concentration and insulin secretion. [19][20][21] However, it has also been reported that the pancreatectomized patients result in a deterioration of insulin secretion and glucose tolerance because of suffering from stress against eating habits such as high glucose or high fat intake. 21) In ITT, the PG concentration of STZ alone group was sustained at the value of over 150 mg/dl and it was significantly higher than that in normal control group at 120 min after injection of insulin (153.7Ϯ37.9 mg/dl, pϽ0.001).…”

Section: Discussionmentioning

confidence: 99%

Establishment and Pathophysiological Characterization of Type 2 Diabetic Mouse Model Produced by Streptozotocin and Nicotinamide

Nakamura

Terajima

Ogata

et al. 2006

Biological & Pharmaceutical Bulletin

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The number of patients with diabetes mellitus, who exhibit insulin resistance, is increasing recently all over the world. 1) The major causes have been suggested to be functional disorders in insulin secreting capacity and in carbohydrate metabolism deterioration with aging. 2,3) In the type 2 diabetic patients without obesity, who have been frequently found in Japanese, Chinese and Korean, the reduction in insulin secretion seems to be more important than the increase in insulin resistance. 4) These defects may be caused by long term hypersecretion of insulin in response to the intake of high calorie food owing to westernized food habits. The hypersecretion of insulin leads to depletion of the insulin stock and hence to the decline in insulin secretion from the pancreatic beta cells.Several kinds of knock-out mice have been recently developed as animal models for diabetes. Although these models express several important molecular pathological features of diabetes, they carry some disadvantages in that they do not exactly express some of the symptoms of type 2 diabetes. Moreover, maintenance of these genetically-modified mice requires intensive managements in large-scaled facilities so that it needs so much cost. In order to overwhelm these disadvantages of genetically-modified model mice, we attempted to establish a type 2 diabetic model with non-obese features mouse by a non-genetic way.Streptozotocin (STZ) is a widely used chemical inducer for type 1 diabetes. 5) STZ has been shown to produce free radicals in the body which specifically cut DNA chains in the pancreatic beta cells, resulting in disorder of the function of pancreatic beta cell and, at a later phase, destruction of the beta cells by necrosis. 6) These processes evoke activation of the poly ADP ribose synthase to repair the damaged DNA, 7) and a large amount of nicotinamide dinucleotide 8) is consumed for this restoration. 9) Here, consumption of NAD is effectively supplemented by intake of nicotinamide (NA). Meanwhile, in some clinical practice, a high dose of NA is occasionally administered to diabetic patients to prevent the progress of insulin-dependent diabetes (IDDM). 10) Type 2 diabetic model in rats with combined application of STZ and NA has been already reported. 11) Thus it was considered that the similar procedures would be applicable for the prevention from STZ-induced excessive destruction of beta cells in mice. We report here the establishment of a novel method for producing non-obese type 2 diabetic mouse model with a non-genetic way, as well as its pathophysiological characterization. We also show that the present mouse model is useful for searching drugs that are beneficial to treatment of the non-obese type 2 diabetes. MATERIALS AND METHODS Animals and DrugsAll animal experiments were carried out according to the "Principles of Laboratory Animal Care" (NIH publication number 85-23, revised 1985) and the Guidelines of the Animal Investigation Committee, Chiba University, Japan.Male C57BL/6J mice of 5-6 week old age were purchas...

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A Study of Glucose Tolerance and Insulin Response in Partially Depancreatized Dogs

Cited by 42 publications

References 0 publications

The effect of hyperglycaemia on pancreatic islets transplanted into rats beneath the kidney capsule

The effect of hyperglycaemia on pancreatic islets transplanted into rats beneath the kidney capsule

Improved outcome of islet transplantation in insulin-treated diabetic mice: effects on beta-cell mass and function

Establishment and Pathophysiological Characterization of Type 2 Diabetic Mouse Model Produced by Streptozotocin and Nicotinamide

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