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Lipid droplets hypertrophy: A crucial determining factor in insulin regulation by adipocytes

Sanjabi, Bahram; Dashty, Monireh; Ozcan, Behiye; Akbarkhanzadeh, Vishtaseb; Rahimi, Mehran; Vinciguerra, Manlio; Van Rooij, Felix; Al-Lahham, Saad; Sheedfar, Fareeba; Van Kooten, Theo G; Spek, C Arnold; Rowshani, Ajda T; Van der Want, Johannes; Klaassen, Rene; Sijbrands, Eric; Peppelenbosch, MP; Rezaee, Farhad
Journal article, Peer reviewed
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URI
http://hdl.handle.net/11250/2178757
Date
2015
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  • Institutt for klinisk og molekylær medisin [1998]
  • Publikasjoner fra CRIStin - NTNU [19694]
Original version
Scientific Reports 2015, 5   10.1038/srep08816
Abstract
Lipid droplets (LDs) hypertrophy in adipocytes is the main cause of energy metabolic system dysfunction,

obesity and its afflictions such as T2D. However, the role of adipocytes in linking energy metabolic disorders

with insulin regulation is unknown in humans. Human adipocytes constitutively synthesize and secrete

insulin, which is biologically functional. Insulin concentrations and release are fat mass- and

LDs-dependent respectively. Fat reduction mediated by bariatric surgery repairs obesity-associated T2D.

The expression of genes, like PCSK1 (proinsulin conversion enzyme),GCG (Glucagon), GPLD1,CD38 and

NNAT, involved in insulin regulation/release were differentially expressed in pancreas and adipose tissue

(AT). INS (insulin) and GCG expression reduced in human AT-T2D as compared to AT-control, but

remained unchanged in pancreas in either state. Insulin levels (mRNA/protein) were higher in AT derived

from prediabetes BB rats with destructed pancreatic b-cells and controls than pancreas derived from the

same rats respectively. Insulin expression in 10 human primary cell types including adipocytes and

macrophages is an evidence for extrapancreatic insulin-producing cells. The data suggest a crosstalk

between AT and pancreas to fine-tune energy metabolic system or may minimize the metabolic damage

during diabetes. This study opens new avenues towards T2D therapy with a great impact on public health.
Publisher
Nature Publishing Group
Journal
Scientific Reports

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