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Preserving Mafa expression in diabetic islet ?-cells improves glycemic control in vivo.

ABSTRACT: The murine Mafa transcription factor is a key regulator of postnatal islet ?-cell activity, affecting insulin transcription, insulin secretion, and ?-cell mass. Human MAFA expression is also markedly decreased in islet ?-cells of type 2 diabetes mellitus (T2DM) patients. Moreover, levels are profoundly reduced in db/db islet ?-cells, a mouse model of T2DM. To examine the significance of this key islet ?-cell-enriched protein to glycemic control under diabetic conditions, we generated transgenic mice that conditionally and specifically produced Mafa in db/db islet ?-cells. Sustained expression of Mafa resulted in significantly lower plasma glucose levels, higher plasma insulin, and augmented islet ?-cell mass. In addition, there was increased expression of insulin, Slc2a2, and newly identified Mafa-regulated genes involved in reducing ?-cell stress, like Gsta1 and Gckr. Importantly, the levels of human GSTA1 were also compromised in T2DM islets. Collectively, these results illustrate how consequential the reduction in Mafa activity is to islet ?-cell function under pathophysiological conditions.

SUBMITTER: Matsuoka TA

PROVIDER: S-EPMC4367268 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Preserving Mafa expression in diabetic islet β-cells improves glycemic control in vivo.

Matsuoka Taka-aki TA Kaneto Hideaki H Kawashima Satoshi S Miyatsuka Takeshi T Tochino Yoshihiro Y Yoshikawa Atsushi A Imagawa Akihisa A Miyazaki Jun-ichi J Gannon Maureen M Stein Roland R Shimomura Iichiro I

The Journal of biological chemistry 20150202 12

The murine Mafa transcription factor is a key regulator of postnatal islet β-cell activity, affecting insulin transcription, insulin secretion, and β-cell mass. Human MAFA expression is also markedly decreased in islet β-cells of type 2 diabetes mellitus (T2DM) patients. Moreover, levels are profoundly reduced in db/db islet β-cells, a mouse model of T2DM. To examine the significance of this key islet β-cell-enriched protein to glycemic control under diabetic conditions, we generated transgenic ...[more]

PMID: 25645923

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Project description:Background:Diabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. This study aims to assess the level of glycemic control and factors contributing to uncontrolled glycemia among diabetic patients at the Nekemte Referral Hospital, West Ethiopia. Methods:A cross sectional study was conducted on diabetic patients attending the diabetes clinic of Nekemte Referral Hospital. A total of 252 study participants were included in the study. Data were collected by interviewing patients during hospital visits and reviewing respective databases. The association between dependent and independent variables was assessed using bivariable and stepwise multivariable logistic regression. A variable with a p-value < 0.05 was considered as an independent predictor. A patient's written informed consent was obtained after explaining the purpose and procedures of the study. Results:Mean age of the participants was 41.7 ± 17.6 years. The majority of the participants (67.1%) had poor knowledge about diabetes. The glycemic rate control was 40.5%; while more than half of the participants (59.5%) had poor glycemic control. On multivariable logistic analysis poor glycemic control was more likely to occur among unemployed (p < 0.001), patients with no family/social support (p = 0.024), duration of diabetes >10 years (p = 0.005), poor knowledge about diabetes (p = 0.012), taking insulin (p = 0.004) and taking metformin plus glibenclamide (p < 0.001). Conclusion:A finding of this study revealed that a glycemic control of study participants was poor. Thus greater effort is needed to improve glycemic control. Health care professionals should work on improving the adherence to anti-diabetic medications of diabetic patients and knowledge of diabetic patients on diabetes by providing education to the patients during follow up to improve glycemic control.

Dataset Information

Preserving Mafa expression in diabetic islet ?-cells improves glycemic control in vivo.

Publications

Preserving Mafa expression in diabetic islet β-cells improves glycemic control in vivo.

Similar Datasets

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