title: Long-acting insulin analog detemir displays reduced effects on adipocyte differentiation of human subcutaneous and visceral adipose stem cells.
abstract: OBJECTIVE
  Since treatment with insulin detemir results in a lower weight gain compared to human insulin, we investigated whether detemir is associated with lower ability to promote adipogenesis and/or lipogenesis in human adipose stem cells (ASC).
  
  
  RESULTS
  Human ASC isolated from both the subcutaneous and visceral adipose tissues were differentiated for 30 days in the presence of human insulin or insulin detemir. Nile Red and Oil-Red-O staining were used to quantify the rate of ASC conversion to adipocytes and lipid accumulation, respectively. mRNA expression levels of early genes, including Fos and Cebpb, as well as of lipogenic and adipogenic genes, were measured at various phases of differentiation by qRT-PCR. Activation of insulin signaling was assessed by immunoblotting. ASC isolated from subcutaneous and visceral adipose tissue were less differentiated when exposed to insulin detemir compared to human insulin, showing lower rates of adipocyte conversion, reduced triglyceride accumulation, and impaired expression of late-phase adipocyte marker genes, such as Pparg2, Slc2a4, Adipoq, and Cidec. However, no differences in activation of insulin receptor, Akt and Erk and induction of the early genes Fos and Cebpb were observed between insulin detemir and human insulin.
  
  
  CONCLUSIONS
  Insulin detemir displays reduced induction of the Pparg2 adipocyte master gene and diminished effects on adipocyte differentiation and lipogenesis in human subcutaneous and visceral ASC, in spite of normal activation of proximal insulin signaling reactions. These characteristics of insulin detemir may be of potential relevance to its weight-sparing effects observed in the clinical setting.
authors.affiliation: Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cignarelli
authors.affiliation: Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Perrini
authors.affiliation: Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Nigro
authors.affiliation: Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Ficarella
authors.affiliation: Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Barbaro
authors.affiliation: Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Peschechera
authors.affiliation: Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Porro
authors.affiliation: Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Natalicchio
authors.affiliation: Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Laviola
authors.affiliation: Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy; Azienda Sanitaria Locale Bari - Ospedale "Sarcone", Terlizzi, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Puglisi
authors.affiliation: Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy. Electronic address: francesco.giorgino@uniba.it.
authors.forename: F
authors.initials: F
authors.lastname: Giorgino
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects*; D050156:Adipogenesis / Q000187:drug effects; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D000069057:Insulin Detemir / Q000494:pharmacology*; D049528:Insulin, Long-Acting / Q000494:pharmacology*; D050152:Intra-Abdominal Fat / Q000166:cytology; D050155:Lipogenesis / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism; D050151:Subcutaneous Fat / Q000166:cytology
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D051017:Apoptosis Regulatory Proteins; D022782:CCAAT-Enhancer-Binding Protein-beta; C545012:CEBPB protein, human; C472088:CIDEC protein, human; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D047495:PPAR gamma; D011506:Proteins; D012333:RNA, Messenger; C495692:SLC2A4 protein, human; D000069057:Insulin Detemir; D051057:Proto-Oncogene Proteins c-akt
keywords: Adipogenesis; Adipose stem cell; Insulin analog; Insulin detemir; Subcutaneous fat; Visceral fat