PMID- 34675005
OWN - NLM
STAT- Publisher
LR  - 20240220
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Linking)
DP  - 2021 Oct 21
TI  - Specific Deletion of CASK in Pancreatic beta Cells Affects Glucose Homeostasis and 
      Improves Insulin Sensitivity in Obese Mice by Reducing Hyperinsulinemia Running 
      Title: beta Cell CASK Deletion Reduces Hyperinsulinemia.
LID - db201208 [pii]
LID - 10.2337/db20-1208 [doi]
AB  - Calcium/calmodulin-dependent serine protein kinase (CASK) is involved in the 
      secretion of insulin vesicles in pancreatic beta-cells. The present study revealed a 
      new in vivo role of CASK in glucose homeostasis during the progression of type 2 
      diabetes mellitus (T2DM). A Cre-loxP system was used to specifically delete the 
      Cask gene in mouse beta-cells (betaCASKKO), and the glucose metabolism was evaluated in 
      betaCASKKO mice fed a normal chow diet (ND) or a high-fat diet (HFD). ND-fed mice 
      exhibited impaired insulin secretion in response to glucose stimulation. 
      Transmission electron microscopy showed significantly reduced numbers of insulin 
      granules at or near the cell membrane in the islets of betaCASKKO mice. By contrast, 
      HFD-fed betaCASKKO mice showed reduced blood glucose and a partial relief of 
      hyperinsulinemia and insulin resistance when compared to HFD-fed wildtype mice. 
      The IRS1/PI3K/AKT signaling pathway was upregulated in the adipose tissue of 
      HFD-betaCASKKO mice. These results indicated that knockout of the Cask gene in beta 
      cells had a diverse effect on glucose homeostasis: reduced insulin secretion in 
      ND-fed mice, but improves insulin sensitivity in HFD-fed mice. Therefore, CASK 
      appears to function in the insulin secretion and contributes to hyperinsulinemia 
      and insulin resistance during the development of obesity-related T2DM.
CI  - (c) 2021 by the American Diabetes Association.
FAU - Liu, Xingjing
AU  - Liu X
AD  - Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, Medical 
      School, Southeast University, Nanjing 210009, China.
FAU - Sun, Peng
AU  - Sun P
AD  - Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of 
      Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing 211166, 
      China.
FAU - Yuan, Qingzhao
AU  - Yuan Q
AD  - Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, Medical 
      School, Southeast University, Nanjing 210009, China.
FAU - Xie, Jinyang
AU  - Xie J
AD  - Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, Medical 
      School, Southeast University, Nanjing 210009, China.
FAU - Xiao, Ting
AU  - Xiao T
AD  - Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, Medical 
      School, Southeast University, Nanjing 210009, China.
FAU - Zhang, Kai
AU  - Zhang K
AD  - Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, Medical 
      School, Southeast University, Nanjing 210009, China.
FAU - Chen, Xiu
AU  - Chen X
AD  - Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, Medical 
      School, Southeast University, Nanjing 210009, China.
FAU - Wang, Yao
AU  - Wang Y
AD  - Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, Medical 
      School, Southeast University, Nanjing 210009, China; 101007985@seu.edu.cn.
FAU - Yuan, Li
AU  - Yuan L
AD  - Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of 
      Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing 211166, 
      China. yuanli@njmu.edu.cn.
FAU - Han, Xiao
AU  - Han X
AD  - Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of 
      Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing 211166, 
      China. hanxiao@njmu.edu.cn.
AD  - State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 
      210023, China.
LA  - eng
PT  - Journal Article
DEP - 20211021
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
SB  - IM
EDAT- 2021/10/23 06:00
MHDA- 2021/10/23 06:00
CRDT- 2021/10/22 05:46
PHST- 2021/10/06 00:00 [received]
PHST- 2021/10/11 00:00 [accepted]
PHST- 2021/10/22 05:46 [entrez]
PHST- 2021/10/23 06:00 [pubmed]
PHST- 2021/10/23 06:00 [medline]
AID - db20-1208 [pii]
AID - 10.2337/db20-1208 [doi]
PST - aheadofprint
SO  - Diabetes. 2021 Oct 21:db201208. doi: 10.2337/db20-1208.