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Loss of beta-cell mass leads to a reduction of pulse mass with normal periodicity, regularity and entrainment of pulsatile insulin secretion in Göttingen minipigs.
MedLine Citation:
PMID:  12627318     Owner:  NLM     Status:  MEDLINE    
AIMS/HYPOTHESIS: Type 2 diabetes is associated with impaired insulin action and secretion, including disturbed pulsatile release. Impaired pulsatility has been related to impaired insulin action, thus providing a possible link between release and action of insulin. Furthermore, progressive loss of beta-cell mass has been implicated in the pathogenesis of Type 2 diabetes. The aim of this study was to evaluate a possible link between loss of beta-cell mass and impaired pulsatile insulin secretion with special focus on glucose responsiveness of insulin secretion. METHODS: The kinetic and dynamic profiles of insulin in Göttingen minipigs are favourable for studies on pulsatility and a model of diabetes with reduced beta-cell mass has recently been established. Pigs were studied before (n=14) and after (n=10) reduction of beta-cell mass by nicotinamide (67 mg/kg) and streptozotocin (125 mg/kg) from 17.7+/-4.7 (normal animals, n=5) to 6.1+/-2.0 mg/kg. Pulsatile insulin secretion was examined during basal (n=8 normal, n=6 beta-cell reduced) and glucose entrained (n=6 normal, n=4 beta-cell reduced) conditions. Insulin concentration time series were analysed by autocorrelation and spectral analyses for periodicities and regularity, and by deconvolution for pulse frequency, mass and amplitude. RESULTS: Reduction of beta-cell mass and secondary hyperglycaemia resulted in correspondingly (r=0.7421, p=0.0275) reduced pulse mass (42% of normal during basal and 31% during entrained conditions) with normal periodicity (6.6+/-2.2 vs 5.8+/-2.4 min, p=0.50), regularity and entrainability of insulin secretion. CONCLUSION/INTERPRETATION: Neither beta-cell loss, nor 2 weeks of slight hyperglycaemia, as seen in the beta-cell-reduced minipig, probably accounts for the disturbed insulin pulsatility observed in human Type 2 diabetes.
M O Larsen; C F Gotfredsen; M Wilken; R D Carr; N Pørksen; B Rolin
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Publication Detail:
Type:  Journal Article     Date:  2003-01-11
Journal Detail:
Title:  Diabetologia     Volume:  46     ISSN:  0012-186X     ISO Abbreviation:  Diabetologia     Publication Date:  2003 Feb 
Date Detail:
Created Date:  2003-03-10     Completed Date:  2003-12-05     Revised Date:  2004-10-05    
Medline Journal Info:
Nlm Unique ID:  0006777     Medline TA:  Diabetologia     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  195-202     Citation Subset:  IM    
Department of Pharmacological Research I, Pharmacology, Research and Development, Novo Allé 6A1.005, 2880 Bagsvaerd, Denmark.
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MeSH Terms
Cell Death
Drug Combinations
Hyperglycemia / metabolism
Insulin / secretion*
Islets of Langerhans / drug effects,  pathology,  physiopathology*
Niacinamide / pharmacology
Pulsatile Flow
Streptozocin / pharmacology
Swine, Miniature
Reg. No./Substance:
0/Drug Combinations; 11061-68-0/Insulin; 18883-66-4/Streptozocin; 98-92-0/Niacinamide
Erratum In:
Diabetologia. 2004 Jan;47(1):155

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