Effect of partial pancreatectomy on diabetic status in BALB/c mice

Hardikar, Anandwardhan A.; Karandikar, Mahesh; Bhonde, Ramesh

doi:10.1677/joe.0.1620189

Cited by 50 publications

(41 citation statements)

References 19 publications

(22 reference statements)

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“…After injury, these cells are thought to first proliferate, then differentiate into b-cells and migrate to form new islets or replenish existing islets. To test this idea we used partial pancreatectomy (Px), an injury model in which regeneration has previously been documented 4,5,12,[26][27][28][29] . We first verified that Px did indeed result in the generation of new b-cells.…”

Section: B-cell Regenerationmentioning

confidence: 99%

Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation

Dor

Brown

Martinez

et al. 2004

Nature

2,112

1,823

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generate and maintain the correct number of cells is a fundamental problem in biology. In principle, tissue turnover can occur by the differentiation of stem cells, as is well documented for blood, skin and intestine, or by the duplication of existing differentiated cells. Recent work on adult stem cells has highlighted their potential contribution to organ maintenance and repair. However, the extent to which stem cells actually participate in these processes in vivo is not clear. Here we introduce a method for genetic lineage tracing to determine the contribution of stem cells to a tissue of interest. We focus on pancreatic b-cells, whose postnatal origins remain controversial. Our analysis shows that pre-existing b-cells, rather than pluripotent stem cells, are the major source of new b-cells during adult life and after pancreatectomy in mice. These results suggest that terminally differentiated b-cells retain a significant proliferative capacity in vivo and cast doubt on the idea that adult stem cells have a significant role in b-cell replenishment.The literature on pancreatic b-cells and islets of Langerhans is replete with studies suggesting various mechanisms for b-cell homeostasis and regenerative repair. Early studies on patterns of [ 3 H]thymidine incorporation indicated that adult pancreatic endocrine cells belong to a class of tissues that could be maintained by the self-duplication of differentiated cells [1][2][3] . More recent immunohistochemical observations suggest a stem-cell origin for islet cells, including insulin-expressing b-cells 4 . It has been proposed that these adult pancreatic stem or progenitor cells reside in the epithelium of pancreatic ducts 5,6 , inside islets 7 or in the bone marrow 8 . Others have suggested that b-cells form in the adult by transdifferentiation of pancreatic acinar cells 9 , islet cells that express hormones other than insulin 10 , or splenocytes 11 . In addition to explaining the formation of new b-cells within existing islets, it has also been suggested that whole new islets form (islet neogenesis) by clustering of new b-cells that are derived from stem cells 5,12,13 . However, all of these models and suggestions are, for the most part, based on the interpretation of static histological data rather than direct lineage analysis 14 .We developed a simple method for distinguishing stem-cellderived b-cells from the progeny of pre-existing b-cells. Fully differentiated b-cells, defined here as post-natal cells transcribing the insulin gene, are heritably labelled in transgenic mice with a tamoxifen-inducible Cre/lox system ('pulse'). The label is the expression of the human alkaline phosphatase protein, which can be detected by a histochemical stain. After a long period, during which turnover occurs ('chase'), b-cells are examined for the presence of the label. Cells generated after the pulse are labelled if and only if they are the progeny of pre-existing (labelled) b-cells; new b-cells derived from any non-b source, including stem cells, are not labelled. Differ...

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Section: B-cell Regenerationmentioning

confidence: 99%

Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation

Dor

Brown

Martinez

et al. 2004

Nature

2,112

1,823

View full text Add to dashboard Cite

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“…A hyperglycemic condition in Pancreatectomised mice occurred due to loss of β-cells. In case of Pancreatectomised group, the reversal of their glycaemic status has occurred probably due to nesidioblastosis (hyperinsulinemic hypoglycaemia due to over function of pancreatic β-cells with an abnormal microscopic exhibition) [10].…”

Section: Discussionmentioning

confidence: 99%

“…For this estimation blood was withdrawn from the tail vein of the animals and evaluations were done on 0 th , 15 th , 30 th , 45 th and 60 th d [10].…”

Section: Fasting Blood Glucose Level Estimationsmentioning

confidence: 99%

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Pre-Clinical Studies on Diabetes Mellitus Using Partial Pancreatectomy in Swiss Albino Mice

Jana

Mazumder

2018

Int J Pharm Pharm Sci

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Objective: The present study was aimed at the development of partial pancreatectomy in a murine model for diabetes. Methods:Diabetes model was successfully developed by partial pancreatectomy method. In this study, cyclosporine was used for influenced the glycaemic status. Diabetes status was evaluated by fasting blood glucose level (FBG), lipid profile (by estimation of total cholesterol level and HDLlevel), serum amylase and biochemical assay like glutathione estimation. Results:We report here the restoration of euglycaemic status in cyclosporine-induced diabetic in swiss albino mice after 30% pancreatectomy. In this study, Pancreatectomised (partial) group of animals showed a rapid elevation of glycaemic status, starting from 15 th post observational d, but the level of significance decreased gradually from 15 th (P<0.01) to 60 th Conclusion:The biochemical and histopathological evaluations suggest that there is the development of the diabetic model in the pancreatectomized group and diabetes status induced by pancreatectomy is curable to a certain extent due to the regeneration of β-cells.(P<0.05) d. This was probably due to nesidioblastotic activity which shifted the fasting blood glucose level towards normoglycaemic status with β-cells regeneration. Cyclosporine treated a group of mice showed normoglycaemic status throughout the whole experimental period, but the cholesterol level remained significant (P<0.001) till the end of the experimental d. Gradually decrements in glycaemia of the diabetic pancreatectomised animals demonstrate islets neogenesis occurring after the operative activity, leading to normoglycaemic condition, probably attributed to β-cells proliferation.

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“…A kind of regeneration or neogenesis of β-cells might occur when the cells are not exposed to glucose-induced stress triggered by hyperglycemia in addition to the inflammatory and/or autoimmune reaction. Such phenomena, together with complete functional recovery, have been observed after experimental induction of endocrine necrosis in the pancreas [25], STZ-induced β-cell death [26], and subtotal pancreatectomy [27], suggesting that pancreatic endocrine tissue is able to renew itself after damage. Physiologically, pregnancy is a well-known model of pancreatic adaptation, resulting in increased β-cell mass that contributes to maternal physiological hyperinsulinemia necessary for placenta and fetal growth.…”

Section: Transient Recovery Of Islet Function In the Prodromal Diabetmentioning

confidence: 91%

Tolerance Induction and Endogenous Regeneration of Pancreatic β-Cells in Established Autoimmune Diabetes

Sia

Homo‐Delarche²

2004

Rev Diab Stud

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■ AbstractStudies aimed at the understanding of the multifactorial development of autoimmune diabetes have made substantial contributions toward elucidating the molecular mechanisms that open the road to an effective prevention of defective immune responses. Immunomodulatory regimens capable of inducing tolerance are shown to be effective even in the reversal of established autoimmune diabetes in animal models. Experimental trials including the reeducation of autoreactive T cells, depletion of macrophages, dendritic cells, and T cells, as well as the use of monoclonal antibodies, have yielded encouraging results, but have not yet been translated into beneficial clinical outcomes. In addition, we are now seeing an emergence of promising new directions aimed at the induction of islet regeneration by endogenous factors, suggesting that the repair of pancreatic tissue is possible without the need for an engraftment of donor tissue. These recent waves of technological progress have injected new hope for a combined therapy to offer diabetic patients longterm benefits of insulin independence. This article reviews the latest findings on diabetic pathogenesis and discusses promising avenues to tolerance induction and islet regeneration.

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Effect of partial pancreatectomy on diabetic status in BALB/c mice

Cited by 50 publications

References 19 publications

Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation

Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation

Pre-Clinical Studies on Diabetes Mellitus Using Partial Pancreatectomy in Swiss Albino Mice

Tolerance Induction and Endogenous Regeneration of Pancreatic β-Cells in Established Autoimmune Diabetes

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