Lipid droplets hypertrophy: a crucial determining factor in insulin regulation by adipocytes.
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 β-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.
Department of Genetics, University Medical Center Groningen, Groningen. The Netherlands.
Bahram
B
Sanjabi
1] Department of Gastroenterology and Hepatology, Erasmus Medical Center, University of Rotterdam, Rotterdam, The Netherlands [2] Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Monireh
M
Dashty
Department of endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands.
Behiye
B
Özcan
Institute Center-45, Medical University of Amsterdam, University of Amsterdam, The Netherlands.
Vishtaseb
V
Akbarkhanzadeh
Faculty of Medical Science, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Mehran
M
Rahimi
1] Institute for Liver and Digestive Health, Division of Medicine, University College London (UCL), London, UK [2] Gastroenterology Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
Manlio
M
Vinciguerra
Department of cardiovascular genetics, Metabolism, Erasmus Medical Center, Rotterdam, The Netherlands.
Felix
F
van Rooij
Department of Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Saad
S
Al-Lahham
1] Department of Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands [2] Department of Physiology, Radboud University Medical Center, Nijmegen, The Netherlands.
Fareeba
F
Sheedfar
Department of Biomedical Engineering, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Theo G
TG
van Kooten
Department for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
C Arnold
CA
Spek
Department of Internal Medicine, section Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, the Netherlands.
Ajda T
AT
Rowshani
Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.
Johannes
J
van der Want
Department of Surgery, Bariatric Surgery, Maas City Hospital, Rotterdam, The Netherlands.
Rene
R
Klaassen
Department of cardiovascular genetics, Metabolism, Erasmus Medical Center, Rotterdam, The Netherlands.
Eric
E
Sijbrands
Department of Gastroenterology and Hepatology, Erasmus Medical Center, University of Rotterdam, Rotterdam, The Netherlands.
Maikel P
MP
Peppelenbosch
1] Department of Gastroenterology and Hepatology, Erasmus Medical Center, University of Rotterdam, Rotterdam, The Netherlands [2] Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Farhad
F
Rezaee
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D066292:Lipid Droplets / Q000378:metabolism* / Q000473:pathology; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats
D015415:Biomarkers; D007328:Insulin; D012333:RNA, Messenger