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Islet insulin secretory patterns in diabetes and the role of UCP2

Lin, Jian-Man, 1961- (författare)
Uppsala universitet,Institutionen för medicinsk cellbiologi
Grill, Valdemar, professor (opponent)
Dept of Medicine,Section Endocrinology,University Hospital of Trondheim, Trondheim
 (creator_code:org_t)
ISBN 9155454674
Uppsala : Acta Universitatis Upsaliensis, 2002
Engelska 37 s.
Serie: Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 0282-7476 ; 1207
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
Abstract Ämnesord
Stäng  
  • During development of type 1 and type 2 diabetes plasma insulin patterns are altered. Since the islet insulin release pattern has been implicated in this development, insulin secretion from single islets was studied and linked to the islet protein levels of uncoupling protein-2 (UCP2). Islets were isolated from NOD- and KKAy- mice, GK- and GK-derived congenic rats, which are animal models of diabetes, and three human subjects with type 2 diabetes. At basal glucose (3 mM), insulin release from such islets was pulsatile and the amount released was comparable to that of control islets. When the glucose concentration was raised to 11 mM insulin release was essentially unchanged in islets isolated from older NOD- and KKAy- mice, GK- and Niddm1i congenic rats, and NIDDM persons. In islets from Niddm1f congenic rats, younger NOD- and KKAy-mice, control animals and normal human donors the secretion rate increased 2-9 fold when the glucose concentration was raised. This rise in secretion was manifested as increase of the amplitude of the insulin oscillations without affecting their frequency. Impaired glucose-induced insulin release was associated with reduction in glucose oxidation measured in NOD-islets, unaffected respiration measured in GK-islets and higher protein level of UCP2 measured in KKAy-islets. When the UCP2 amounts in KKAy-islets were reduced by culture to those of control islets, glucose-induced insulin secretion was essentially normalized. Our studies suggest that the deranged plasma insulin patterns observed in diabetes are related to decrease in the amplitude of insulin oscillations from the islets rather than loss of the oscillatory activity. This reduction of pulse amplitude may be related to impaired glucose metabolism and/or increased mitochondrial uncoupling.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

Cell biology
type 1 diabetes
type 2 diabetes
NOD
GK
congenes
KKAy
human
islet
glucose
insulin release
oscillation
frequency
amplitude
oxidation
respiration
UCP2
western blot
Cellbiologi
Cell biology
Cellbiologi
medicinsk cellbiologi
Medical Cell Biology

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