PMID- 24092547
OWN - NLM
STAT- MEDLINE
DCOM- 20140127
LR  - 20220331
IS  - 1479-683X (Electronic)
IS  - 0804-4643 (Linking)
VI  - 170
IP  - 1
DP  - 2014 Jan
TI  - Inflammatory adipokines contribute to insulin resistance in active acromegaly and 
      respond differently to different treatment modalities.
PG  - 39-48
LID - 10.1530/EJE-13-0523 [doi]
AB  - BACKGROUND: Active acromegaly is associated with insulin resistance, but it is 
      uncertain whether inflammation in adipose tissue is a contributing factor. AIM: 
      To test if GH/IGF1 promotes inflammation in adipocytes, and if this is relevant 
      for systemic insulin resistance in acromegaly. Furthermore, to investigate the 
      effect of treatment modalities (transsphenoidal surgery (TS), somatostatin 
      analogs (SAs), and pegvisomant (PGV)) on glucose metabolism and inflammatory 
      biomarkers in acromegaly. METHODS: The in vitro effects of GH/IGF1 on gene 
      expression of adipokines in human adipocytes were investigated. Body composition, 
      glucose metabolism, and circulating adipokines (adiponectin (AD), high-molecular 
      weight AD (HMWAD), leptin, vascular endothelial growth factor-A (VEGF-A), 
      monocyte chemotactic protein 1 (MCP1), and thioredoxin (TRX)) were measured in 37 
      patients with active acromegaly before and after treatment. RESULTS: In vitro GH, 
      but not IGF1, increased VEGF and MCP1 in human adipocytes. In all treatment 
      groups, body fat increased and IGF1 decreased to the same extent. Fasting glucose 
      decreased in the TS (P=0.016) and PGV (P=0.042) groups, but tended to increase in 
      the SA group (P=0.078). Insulin and HOMA-IR decreased in both TS and SA groups, 
      while the PGV group showed no changes. Serum VEGF and MCP1 decreased 
      significantly in the TS group only (P=0.010, P=0.002), while HMWAD increased with 
      PGV treatment only (P=0.018). A multivariate analysis model identified the 
      changes in GH and VEGF as predictors of improvement in HOMA-IR after treatment 
      (R(2)=0.39, P=0.002). CONCLUSIONS: i) GH directly promotes inflammation of human 
      adipocytes by increasing VEGF and MCP1 levels; ii) glucose metabolism and 
      inflammation (VEGF and MCP1) improve to some extent after treatment, despite an 
      increase in adipose tissue mass; and iii) the decrease in insulin resistance 
      after therapy in acromegaly depends, to some extent, on treatment modalities.
FAU - Olarescu, Nicoleta C
AU  - Olarescu NC
AD  - Section of Specialized Endocrinology, Department of Endocrinology.
FAU - Ueland, Thor
AU  - Ueland T
FAU - Godang, Kristin
AU  - Godang K
FAU - Lindberg-Larsen, Rune
AU  - Lindberg-Larsen R
FAU - Jorgensen, Jens Otto L
AU  - Jorgensen JO
FAU - Bollerslev, Jens
AU  - Bollerslev J
LA  - eng
SI  - ClinicalTrials.gov/NCT00521300
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20131122
PL  - England
TA  - Eur J Endocrinol
JT  - European journal of endocrinology
JID - 9423848
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Recombinant Proteins)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (sandostatinLAR)
RN  - 12629-01-5 (Human Growth Hormone)
RN  - 51110-01-1 (Somatostatin)
RN  - N824AOU5XV (pegvisomant)
RN  - RWM8CCW8GP (Octreotide)
SB  - IM
MH  - Acromegaly/drug therapy/immunology/*metabolism/surgery
MH  - Adiposity/drug effects
MH  - Adult
MH  - Cells, Cultured
MH  - Chemokine CCL2/blood/genetics/metabolism
MH  - Cohort Studies
MH  - Female
MH  - *Gene Expression Regulation/drug effects
MH  - Human Growth Hormone/analogs & derivatives/antagonists & 
      inhibitors/genetics/*metabolism/therapeutic use
MH  - Humans
MH  - Inflammation Mediators/blood/*metabolism
MH  - *Insulin Resistance
MH  - Intra-Abdominal Fat/cytology/drug effects/immunology/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Octreotide/analogs & derivatives/therapeutic use
MH  - Prospective Studies
MH  - Recombinant Proteins/metabolism
MH  - Somatostatin/analogs & derivatives/therapeutic use
MH  - Subcutaneous Fat/cytology/drug effects/immunology/*metabolism
MH  - Vascular Endothelial Growth Factor A/blood/genetics/metabolism
EDAT- 2013/10/05 06:00
MHDA- 2014/01/28 06:00
CRDT- 2013/10/05 06:00
PHST- 2013/10/05 06:00 [entrez]
PHST- 2013/10/05 06:00 [pubmed]
PHST- 2014/01/28 06:00 [medline]
AID - EJE-13-0523 [pii]
AID - 10.1530/EJE-13-0523 [doi]
PST - epublish
SO  - Eur J Endocrinol. 2013 Nov 22;170(1):39-48. doi: 10.1530/EJE-13-0523. Print 2014 
      Jan.