PMID- 26105159
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20181217
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 117
IP  - 1
DP  - 2016 Jan
TI  - The Paradoxical Effects of AMPK on Insulin Gene Expression and Glucose-Induced 
      Insulin Secretion.
PG  - 239-46
LID - 10.1002/jcb.25271 [doi]
AB  - The activation of AMP-activated protein kinase (AMPK) is known to repress the 
      expression of the insulin gene and glucose-stimulated insulin secretion (GSIS). 
      However, the mechanisms by which this occurs, as well as the effects of AMPK 
      activation on glucolipotoxicity-induced beta-cell dysfunction, have not been 
      elucidated. To investigate the effects of 5-amino-4-imidazolecarboxamide 
      ribonucleotide (AICAR) and peroxisome proliferator-activated 
      receptorgamma-coactivator-1alpha (PGC-1alpha) on beta-cell-specific genes under glucolipotoxic 
      conditions, we performed real-time PCR and measured insulin secretion by primary 
      islets. To study these effects in vivo, we administered AICAR for 10 days (1 mg/g 
      body weight) to 90% pancreatectomized hyperglycemic mice. The exposure of 
      isolated rat and human islets to glucolipotoxic conditions and the overexpression 
      of PGC-1alpha suppressed insulin and NEUROD1 mRNA expression. However, the expression 
      of these genes was preserved by AICAR treatment and by PGC-1alpha inhibition. 
      Exposure of isolated islets to glucolipotoxic conditions for 3 days decreased 
      GSIS, which was also well maintained by AICAR treatment and by PGC-1alpha inhibition. 
      The administration of AICAR to 90% pancreatectomized hyperglycemic mice improved 
      glucose tolerance and insulin secretion. These results indicate that treatment of 
      islets with an AMPK agonist under glucolipotoxic conditions protects against 
      glucolipotoxicity-induced beta-cell dysfunction. A better understanding of the 
      functions of molecules such as PGC-1alpha and AMPK, which play key roles in 
      intracellular fuel regulation, could herald a new era for the treatment of 
      patients with type 2 diabetes mellitus by providing protection against 
      glucolipotoxicity.
CI  - (c) 2015 Wiley Periodicals, Inc.
FAU - Kim, Ji-Won
AU  - Kim JW
AD  - Department of Endocrinology & Metabolism, The Catholic University of Korea, 
      Seoul, 137-040, Korea.
FAU - You, Young-Hye
AU  - You YH
AD  - Department of Endocrinology & Metabolism, The Catholic University of Korea, 
      Seoul, 137-040, Korea.
FAU - Ham, Dong-Sik
AU  - Ham DS
AD  - Department of Endocrinology & Metabolism, The Catholic University of Korea, 
      Seoul, 137-040, Korea.
FAU - Yang, Hae Kyung
AU  - Yang HK
AD  - Department of Endocrinology & Metabolism, The Catholic University of Korea, 
      Seoul, 137-040, Korea.
FAU - Yoon, Kun-Ho
AU  - Yoon KH
AD  - Department of Endocrinology & Metabolism, The Catholic University of Korea, 
      Seoul, 137-040, Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Insulin)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Ppargc1a protein, mouse)
RN  - 0 (Ribonucleotides)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - F0X88YW0YK (AICA ribonucleotide)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Aminoimidazole Carboxamide/analogs & derivatives/pharmacology
MH  - Animals
MH  - Glucose/*pharmacology
MH  - Insulin/*metabolism
MH  - Insulin Secretion
MH  - Insulin-Secreting Cells/drug effects/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/drug 
      effects/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Ribonucleotides/pharmacology
OTO - NOTNLM
OT  - AICAR
OT  - AMPK
OT  - GLUCOLIPOTOXICITY
OT  - PGC-1alpha
OT  - TYPE 2 DIABETES MELLITUS
EDAT- 2015/06/25 06:00
MHDA- 2016/12/15 06:00
CRDT- 2015/06/25 06:00
PHST- 2015/02/03 00:00 [received]
PHST- 2015/06/19 00:00 [accepted]
PHST- 2015/06/25 06:00 [entrez]
PHST- 2015/06/25 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
AID - 10.1002/jcb.25271 [doi]
PST - ppublish
SO  - J Cell Biochem. 2016 Jan;117(1):239-46. doi: 10.1002/jcb.25271.