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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http://hdl.handle.net/11250/2178757Utgivelsesdato
2015Metadata
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Sammendrag
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.