title: Islet amyloid polypeptide acts on glucose- stimulated beta cells to reduce voltage-gated calcium channel activation, intracellular Ca(2+) concentration, and insulin secretion.
abstract: OBJECTIVE
  the mechanism by which islet amyloid polypeptide (IAPP) inhibits insulin release is unclear. We hypothesized that reduced voltage-gated calcium channel activity and intracellular Ca(2+) concentration might contribute to IAPP-mediated inhibition of glucose-stimulated insulin release.
  
  
  METHODS
  rat islet beta cells were cultured and treated with various extracellular concentrations of IAPP, and insulin release was stimulated via addition of glucose. Activation voltage, high voltage-gated calcium channel currents, intracellular Ca(2+) concentration, and insulin secretion were detected by patch clamp electrophysiology, fluorescent digital imaging microscopy using calcium-sensitive fluorescent dye, and radioimmunoassay, respectively.
  
  
  RESULTS
  high voltage-gated calcium channel currents, intracellular Ca(2+) concentration, and insulin secretion increased in a dose-dependent manner when rat beta cells were exposed to glucose. After short-term IAPP treatment (5 or 10 µM), these parameters decreased significantly in glucose-stimulated beta cells. However, no significant changes were observed with lower doses of IAPP.
  
  
  CONCLUSIONS
  glucose-stimulated islet beta-cell high voltage-gated calcium channels were activated in conjunction with insulin secretion, while high extracellular concentrations of IAPP inhibited beta-cell high voltage-gated calcium channel activation and insulin secretion in a dose-dependent manner.
authors.affiliation: Department of Endocrinology, Institute of Endocrinology, Tianjin Medical University, Affiliated General Hospital, Tianjin, China. zhutiehong@yahoo.com.cn
authors.forename: Tiehong
authors.initials: T
authors.lastname: Zhu
authors.forename: Yinxia
authors.initials: Y
authors.lastname: Wang
authors.forename: Bingjun
authors.initials: B
authors.lastname: He
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zang
authors.forename: Qing
authors.initials: Q
authors.lastname: He
authors.forename: Weihua
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001067:Appetite Depressants / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002478:Cells, Cultured; D004594:Electrophysiology; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism*; D058228:Islet Amyloid Polypeptide / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013549:Sweetening Agents / Q000494:pharmacology
chemical_list: D001067:Appetite Depressants; D015220:Calcium Channels; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D013549:Sweetening Agents; D005947:Glucose; D002118:Calcium