Pathogenesis of Type 1 Diabetes Mellitus and Rodent Experimental Models

Gvazava, I. G.; Rogovaya, O. S.; Borisov, M A; Vorotelyak, E. A.; Vasiliev, A. V.

doi:10.32607/20758251-2018-10-1-24-33

Cited by 41 publications

(22 citation statements)

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“…Since it targets the pancreatic β cells, the STZ-induced diabetes is often considered to be the most suitable model for T1DM. Although there were several limitations, such as possible toxic effects to other organs/cell types, STZ is still the most widely used model for T1DM [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Treatment with Mammalian Ste-20-like Kinase 1/2 (MST1/2) Inhibitor XMU-MP-1 Improves Glucose Tolerance in Streptozotocin-Induced Diabetes Mice

et al. 2020

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Diabetes mellitus (DM) is one of the major causes of death in the world. There are two types of DM—type 1 DM and type 2 DM. Type 1 DM can only be treated by insulin injection whereas type 2 DM is commonly treated using anti-hyperglycemic agents. Despite its effectiveness in controlling blood glucose level, this therapeutic approach is not able to reduce the decline in the number of functional pancreatic β cells. MST1 is a strong pro-apoptotic kinase that is expressed in pancreatic β cells. It induces β cell death and impairs insulin secretion. Recently, a potent and specific inhibitor for MST1, called XMU-MP-1, was identified and characterized. We hypothesized that treatment with XMU-MP-1 would produce beneficial effects by improving the survival and function of the pancreatic β cells. We used INS-1 cells and STZ-induced diabetic mice as in vitro and in vivo models to test the effect of XMU-MP-1 treatment. We found that XMU-MP-1 inhibited MST1/2 activity in INS-1 cells. Moreover, treatment with XMU-MP-1 produced a beneficial effect in improving glucose tolerance in the STZ-induced diabetic mouse model. Histological analysis indicated that XMU-MP-1 increased the number of pancreatic β cells and enhanced Langerhans islet area in the severe diabetic mice. Overall, this study showed that MST1 could become a promising therapeutic target for diabetes mellitus.

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Section: Discussionmentioning

confidence: 99%

Treatment with Mammalian Ste-20-like Kinase 1/2 (MST1/2) Inhibitor XMU-MP-1 Improves Glucose Tolerance in Streptozotocin-Induced Diabetes Mice

et al. 2020

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“…In STZ-induced diabetic rats, application of 2% and 4% but not 1% lidocaine resulted in nerve oedema, degeneration and demyelination of myelinated nerve fibres. [18]. These data led to the teaching that the risk for local anaesthetic-induced nerve injury could be higher in animals and subjects with diabetic neuropathy [4].…”

Section: Discussionmentioning

confidence: 99%

“…Six weeks old C57BL/6J-OlaHsd female mice (n = 36, weight 25-30 g) were obtained from Harlan Laboratories -Envigo (Italy) and reared at the Centre for Laboratory At the age of 8 weeks, after 2 weeks of quarantine and acclimatization period with free access to clean water and standardized diet (Mucedola, Milan, Italy), diabetes type 1 was induced in mice by intraperitoneal injection of 200 mg kg − 1 STZ in accordance with the protocols for achieving STZ-induced diabetes in mice [27,35]. STZ is an alkylating agent that induces degeneration in pancreatic β islets [18,36]. Diabetes was confirmed by measuring a fasting glucose level using Bayer Contour glucose meter (Ascensia Diabetes Care Holdings AG, Switzerland) three weeks after STZ injection.…”

Section: Animal Housing and Induction/confirmation Of Diabetesmentioning

confidence: 99%

Neurotoxicity of bupivacaine and liposome bupivacaine after sciatic nerve block in healthy and streptozotocin-induced diabetic mice

et al. 2020

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Background: Long-acting local anaesthetics (e.g. bupivacaine hydrochloride) or sustained-release formulations of bupivacaine (e.g. liposomal bupivacaine) may be neurotoxic when applied in the setting of diabetic neuropathy. The aim of the study was to assess neurotoxicity of bupivacaine and liposome bupivacaine in streptozotocin (STZ)induced diabetic mice after sciatic nerve block. We used the reduction in fibre density and decreased myelination assessed by G-ratio (defined as axon diameter divided by large fibre diameter) as indicators of local anaesthetic neurotoxicity. Results: Diabetic mice had higher plasma levels of glucose (P < 0.001) and significant differences in the tail flick and plantar test thermal latencies compared to healthy controls (P < 0.001). In both diabetic and nondiabetic mice, sciatic nerve block with 0.25% bupivacaine HCl resulted in a significantly greater G-ratio and an axon diameter compared to nerves treated with 1.3% liposome bupivacaine or saline (0.9% sodium chloride) (P < 0.01). Moreover, sciatic nerve block with 0.25% bupivacaine HCl resulted in lower fibre density and higher large fibre and axon diameters compared to the control (untreated) sciatic nerves in both STZ-induced diabetic (P < 0.05) and nondiabetic mice (P < 0.01). No evidence of acute or chronic inflammation was observed in any of the treatment groups. Conclusions: In our exploratory study the sciatic nerve block with bupivacaine HCl (7 mg/kg), but not liposome bupivacaine (35 mg/kg) or saline, resulted in histomorphometric indices of neurotoxicity. Histologic findings were similar in diabetic and healthy control mice.

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“…The evaluation of in vivo efficacy is best tested in animal model systems as this enables testing of effects on the integrated physiological responses. Animal models include diet induced and genetic models of obesity of relevance to T2DM (Al-awar et al, 2016) and the streptozotocin (STZ) induced diabetic model used to study impacts on T1DM efficacy (Gvazava et al, 2018). These are thought to be of more direct relevance to therapeutic outcomes for metabolic disease in humans.…”

Section: Challenge Of Clinically Proven Rākau Rongoammentioning

confidence: 99%

The Potential of Anti-Diabetic Rākau Rongoā (Māori Herbal Medicine) to Treat Type 2 Diabetes Mellitus (T2DM) Mate Huka: A Review

Koia

Shepherd

2020

Front. Pharmacol.

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T2DM (type 2 diabetes mellitus, or Maōri term "mate huka") is a major long-term health issue in New Zealand particularly among the Maōri community. Non-insulin drugs commonly used in New Zealand for the treatment of T2DM have limits to their efficacy as well as side effects, which are of concern for diabetics. As such, the potential for natural products such as traditional rakau rongoāare of interest for potentially preventing the development of T2DM or improving the treatment of the disease. In particular, antidiabetic effects have been reported for rakau rongoāsuch as karamu, kumarahou, and kawakawa. Natural products have been identified in karamu, kumarahou, and kawakawa that have documented potential effects on glucose metabolism that could contribute to the anti-diabetic effect of these rakau rongoa. As such, this could provide scientific insight into the matauranga (traditional knowledge) developed over generations by Maōri. However, detailed laboratory based and clinical studies would be required to understand and validate these properties of karamu, kumarahou, and kawakawa, and to understand how they can be used in T2DM treatment. Social determinants of indigenous health such as language, culture, traditional knowledge, and identity, are important in understanding the relationship Maōri have with their land and the matauranga they developed of the medicinal properties within their rakau rongoa, over many centuries. Interestingly, traditional Maōri views towards scientific research using animal models to test rakau rongoāare varied but supportive. Furthermore, cultural issues surrounding Maōri mana motuhake (self-determination) of traditional rongoāMaōri healing practices and the inequity faced by many kairongoā(rongoāMaōri practitioners) and tohunga (healers) compared to mainstream health are a current issue within the New Zealand health system. As such, a cultural holistic approach for T2DM care among Maōri would be advantageous. This review will outline the available evidence supporting the anti-diabetic efficacy of karamu, kumarahou, and kawakawa. Currently though there is a lack of molecular research to understand the mechanisms of this efficacy, as such this review will

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Pathogenesis of Type 1 Diabetes Mellitus and Rodent Experimental Models

Cited by 41 publications

References 100 publications

Treatment with Mammalian Ste-20-like Kinase 1/2 (MST1/2) Inhibitor XMU-MP-1 Improves Glucose Tolerance in Streptozotocin-Induced Diabetes Mice

Treatment with Mammalian Ste-20-like Kinase 1/2 (MST1/2) Inhibitor XMU-MP-1 Improves Glucose Tolerance in Streptozotocin-Induced Diabetes Mice

Neurotoxicity of bupivacaine and liposome bupivacaine after sciatic nerve block in healthy and streptozotocin-induced diabetic mice

The Potential of Anti-Diabetic Rākau Rongoā (Māori Herbal Medicine) to Treat Type 2 Diabetes Mellitus (T2DM) Mate Huka: A Review

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