Effect of Oral Insulin on Diabetes-Induced Intestinal Mucosal Growth in Rats

Sukhotnik, Igor; Shamir, Raanan; Bashenko, Yulia; Chemodanov, Elena; Shaoul, Ron; Coran, Arnold G.; Shehadeh, Naim

doi:10.1007/s10620-011-1654-6

Cited by 14 publications

(12 citation statements)

References 31 publications

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“…The macromolecule insulin is digested in the lumen of the gut to avoid absorption into the blood stream; however, there is some evidence that oral insulin treatment decreases bw, cholesterol and the triglyceride blood level in different animal models 22 , 33 . In insulin-resistant states, the intestine significantly enhances the production of lipoproteins 34 and glucose 35 .…”

Section: Discussionmentioning

confidence: 99%

“…In insulin-resistant states, the intestine significantly enhances the production of lipoproteins 34 and glucose 35 . The mechanism by which luminal insulin influences intestinal metabolism even without being absorbed is not completely understood, but its capacity to downregulate gut insulin receptor expression 33 might be the cornerstone factor.…”

Section: Discussionmentioning

confidence: 99%

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Maternal low intensity physical exercise prevents obesity in offspring rats exposed to early overnutrition

Ribeiro

Tófolo

Martins

et al. 2017

Sci Rep

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Low intensity exercise during pregnancy and lactation may create a protective effect against the development of obesity in offspring exposed to overnutrition in early life. To test these hypotheses, pregnant rats were randomly assigned into 2 groups: Sedentary and Exercised, low intensity, on a rodent treadmill at 30% VO2Max /30-minute/session/3x/week throughout pregnancy and the lactation. Male offspring were raised in small litters (SL, 3 pups/dam) and normal litters (NL, 9 pups/dam) as models of early overnutrition and normal feed, respectively. Exercised mothers showed low mesenteric fat pad stores and fasting glucose and improved glucose-insulin tolerance, VO2max during lactation and sympathetic activity. Moreover, the breast milk contained elevated levels of insulin. In addition, SL of sedentary mothers presented metabolic dysfunction and glucose and insulin intolerance and were hyperglycemic and hyperinsulinemic in adulthood. SL of exercised mothers showed lower fat tissue accretion and improvements in glucose tolerance, insulin sensitivity, insulinemia and glycemia. The results suggest that maternal exercise during the perinatal period can have a possible reprogramming effect to prevent metabolic dysfunction in adult rat offspring exposed to early overnutrition, which may be associated with the improvement in maternal health caused by exercise.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Maternal low intensity physical exercise prevents obesity in offspring rats exposed to early overnutrition

Ribeiro

Tófolo

Martins

et al. 2017

Sci Rep

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“…Interestingly, oral insulin reduces the diabetes-induced mucosal hypertrophy observed in STZ-treated rats, 27 raising the possibility that hepatic insulin may be secreted into the bile of HIGT-treated mice and restrict bowel growth. However, this remains speculation.…”

Section: Discussionmentioning

confidence: 99%

Hepatic insulin gene therapy prevents diabetic enteropathy in STZ-treated CD-1 mice

You

Anitha

deSouza

et al. 2015

Molecular Therapy - Methods & Clinical Development

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Depending on the population examined, from 6 to 83% of people with diabetes mellitus exhibit symptoms of altered gut motility, manifesting as dysphagia, reflux, early satiety, nausea, abdominal pain, diarrhea, or constipation. Hyperglycemia-induced cell loss within the enteric nervous system has been demonstrated in both diabetic rodents and patients with diabetes. Glycemic control is recommended to prevent diabetic gastroenteropathy but is often difficult to achieve with current treatment modalities. We asked if hepatic insulin gene therapy (HIGT) could inhibit the development of diabetic gastroenteropathy in mice. Bowel length, bowel transit, colonic muscle relaxation, and the numbers of both stimulatory and inhibitory neurons in the colonic myenteric plexus were compared in groups of diabetic mice (DM), control nondiabetic mice (Con), and diabetic mice treated with HIGT (HIGT). Delivery of a metabolically responsive insulin transgene to the liver of STZ-diabetic mice with an adeno-associated virus, sero-type 8 (AAV8) produced near-normal blood sugars for over 1 month and prevented anatomic, functional, and neurohistologic changes observed in diabetic mice. We conclude that in addition to normalizing oxidative metabolism in diabetic rodents, HIGT is sufficient to prevent the development of diabetic gastroenteropathy.

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“…We have shown recently that experimental diabetes results in a significant increase in epithelial cell proliferation and a concomitant increase in cells, indicating accelerated cell turnover within the gastrointestinal tract (Sukhotnik et al 2011). The current study is an extension of our previous work and was designed to investigate the role of Wnt/b-catenin signaling in the development of diabetesinduced intestinal mucosal hyperplasia in a rat model.…”

Section: Introductionmentioning

confidence: 88%

Enhanced intestinal epithelial cell proliferation in diabetic rats correlates with β-catenin accumulation

Dorfman¹,

Pollak²,

Sohotnik³

et al. 2015

Journal of Endocrinology

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The Wnt/b-catenin signaling cascade is implicated in the control of stem cell activity, cell proliferation, and cell survival of the gastrointestinal epithelium. Recent evidence indicates that the Wnt/b-catenin pathway is activated under diabetic conditions. The purpose of this study was to evaluate the role of Wnt/b-catenin signaling during diabetes-induced enteropathy in a rat model. Male rats were divided into three groups: control rats received injections of vehicle; diabetic rats received injections of one dose of streptozotocin (STZ); and diabetic-insulin rats received injections of STZ and were treated with insulin given subcutaneously at a dose of 1 U/kg twice daily. Rats were killed on day 7. Wnt/b-catenin-related genes and expression of proteins was determined using real-time PCR, western blotting, and immunohistochemistry. Among 13 genes identified by real-time PCR, seven genes were upregulated in diabetic rats compared with control animals including the target genes c-Myc and Tcf4. Diabetic rats also showed a significant increase in b-catenin protein compared with control animals. Treatment of diabetic rats attenuated the stimulating effect of diabetes on intestinal cell proliferation and Wnt/b-catenin signaling. In conclusion, enhanced intestinal epithelial cell proliferation in diabetic rats correlates with b-catenin accumulation.

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Effect of Oral Insulin on Diabetes-Induced Intestinal Mucosal Growth in Rats

Abstract: Experimental STZ-induced diabetes causes intestinal mucosal growth and enhances enterocyte turnover in a rat model. OI administration diminishes diabetes-accelerated cell turnover and diabetes-induced mucosal hyperplasia.

Cited by 14 publications

References 31 publications

Maternal low intensity physical exercise prevents obesity in offspring rats exposed to early overnutrition

Maternal low intensity physical exercise prevents obesity in offspring rats exposed to early overnutrition

Hepatic insulin gene therapy prevents diabetic enteropathy in STZ-treated CD-1 mice

Enhanced intestinal epithelial cell proliferation in diabetic rats correlates with β-catenin accumulation

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