PMID- 16901933
OWN - NLM
STAT- MEDLINE
DCOM- 20070410
LR  - 20161124
IS  - 0952-5041 (Print)
IS  - 0952-5041 (Linking)
VI  - 37
IP  - 1
DP  - 2006 Aug
TI  - Metformin reduces lipolysis in primary rat adipocytes stimulated by tumor 
      necrosis factor-alpha or isoproterenol.
PG  - 175-83
AB  - In patients with type 2 non-insulin-dependent diabetes mellitus (NIDDM), the 
      biguanide, metformin, exerts its antihyperglycemic effect by improving insulin 
      sensitivity, which is associated with decreased level of circulating free fatty 
      acids (FFA). The flux of FFA and glycerol from adipose tissue to the blood stream 
      primarily depends on the lipolysis of triacylglycerols in the adipocytes. 
      Adipocyte lipolysis is physiologically stimulated by catecholamine hormones. 
      Tumor necrosis factor-alpha (TNF-alpha), a cytokine largely expressed in adipose 
      tissue, stimulates chronic lipolysis, which may be associated with increased 
      systemic FFA and insulin resistance in obesity and NIDDM. In this study, we 
      examined the role of metformin in inhibiting lipolytic action upon various 
      lipolytic stimulations in primary rat adipocytes. Treatment with metformin 
      attenuated TNF-alpha-mediated lipolysis by suppressing phosphorylation of 
      extracellular signal-related kinase 1/2 and reversing the downregulation of 
      perilipin protein in TNF-alpha-stimulated adipocytes. The acute lipolytic 
      response to adrenergic stimulation of isoproterenol was also restricted by 
      metformin. A high concentration of glucose in the adipocyte culture promoted the 
      basal rate of glycerol release and significantly enhanced the lipolytic action 
      stimulated by either TNF-alpha or isoproterenol. Metformin not only inhibits the 
      basal lipolysis simulated by high glucose, but also suppresses the high 
      glucose-enhanced lipolysis response to TNF-alpha or isoproterenol. The 
      antilipolytic action in adipocytes could be the mechanism by which cellular 
      action by metformin reduces systemic FFA concentration and thus improves insulin 
      sensitivity in obese patients and the hyperglycemic conditions of NIDDM.
FAU - Ren, Tingting
AU  - Ren T
AD  - Department of Physiology and Pathophysiology, Peking University Health Science 
      Center, 38 Xueyuan Road, Beijing 100083, China.
FAU - He, Jinhan
AU  - He J
FAU - Jiang, Hongfeng
AU  - Jiang H
FAU - Zu, Luxia
AU  - Zu L
FAU - Pu, Shenshen
AU  - Pu S
FAU - Guo, Xiaohui
AU  - Guo X
FAU - Xu, Guoheng
AU  - Xu G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Mol Endocrinol
JT  - Journal of molecular endocrinology
JID - 8902617
RN  - 0 (Adrenergic beta-Agonists)
RN  - 0 (Carrier Proteins)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Perilipin-1)
RN  - 0 (Phosphoproteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9100L32L2N (Metformin)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - IY9XDZ35W2 (Glucose)
RN  - L628TT009W (Isoproterenol)
SB  - IM
MH  - Adipocytes/cytology/*drug effects/*metabolism
MH  - Adrenergic beta-Agonists/pharmacology
MH  - Animals
MH  - Carrier Proteins
MH  - Cells, Cultured
MH  - Glucose/metabolism
MH  - Humans
MH  - Hypoglycemic Agents/metabolism
MH  - Isoproterenol/*pharmacology
MH  - Lipolysis/*physiology
MH  - Metformin/*metabolism
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Perilipin-1
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 2006/08/12 09:00
MHDA- 2007/04/11 09:00
CRDT- 2006/08/12 09:00
PHST- 2006/08/12 09:00 [pubmed]
PHST- 2007/04/11 09:00 [medline]
PHST- 2006/08/12 09:00 [entrez]
AID - 37/1/175 [pii]
AID - 10.1677/jme.1.02061 [doi]
PST - ppublish
SO  - J Mol Endocrinol. 2006 Aug;37(1):175-83. doi: 10.1677/jme.1.02061.