title: Islet-enriched gene expression and glucose-induced insulin secretion in human and mouse islets.
abstract: OBJECTIVE
  Our understanding of the transcription factors that control the development and function of rodent islet beta cells is advancing rapidly, yet less is known of the role they play in similar processes in human islets.
  
  
  METHODS
  To characterise the abundance and regulation of key proteins involved in glucose-regulated insulin secretion in human islets, we examined the expression of MAFA, MAFB, GLUT2 (also known as SLC2A2), βGK (also known as GCK) and PDX1 in isolated, highly purified human islets with an intact insulin secretory pattern. We also assessed these features in islets from two different mouse strains (C57BL/6J and FVB).
  
  
  RESULTS
  Compared with mouse islets, human islets secreted more insulin at baseline glucose (5.6 mmol/l), but less upon stimulation with high glucose (16.7 mmol/l) or high glucose plus 3-isobutyl-1-methyl-xanthine. Human islets had relatively more MAFB than PDX1 mRNA, while mouse islets had relatively more Pdx1 than Mafb mRNA. However, v-maf musculoaponeurotic fibrosarcoma oncogene homologue (MAF) B protein was found in human islet alpha and beta cells. This is unusual as this regulator is only produced in islet alpha cells in adult mice. The expression of insulin, MAFA, βGK and PDX1 was not glucose-regulated in human islets with an intact insulin secretory pattern.
  
  
  CONCLUSIONS
  Our results suggest that human islets have a distinctive distribution and function of key regulators of the glucose-stimulated insulin secretion pathway, emphasising the urgent need to understand the processes that regulate human islet beta cell function.
authors.affiliation: Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University, 7435 MRBIV Nashville, TN 37232, USA.
authors.forename: C
authors.initials: C
authors.lastname: Dai
authors.forename: M
authors.initials: M
authors.lastname: Brissova
authors.forename: Y
authors.initials: Y
authors.lastname: Hang
authors.forename: C
authors.initials: C
authors.lastname: Thompson
authors.forename: G
authors.initials: G
authors.lastname: Poffenberger
authors.forename: A
authors.initials: A
authors.lastname: Shostak
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: R
authors.initials: R
authors.lastname: Stein
authors.forename: A C
authors.initials: AC
authors.lastname: Powers
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051258:MafB Transcription Factor / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D055571:Secretory Pathway / Q000187:drug effects; D013045:Species Specificity; D046509:Tissue Culture Techniques; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D018398:Homeodomain Proteins; D007328:Insulin; D051258:MafB Transcription Factor; D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein