Sökning: WFRF:(Ekelund Mats) >
TPN-evoked dysfunct...
TPN-evoked dysfunction of islet lysosomal activity mediates impairment of glucose-stimulated insulin release
-
- Salehi, S Albert (författare)
- Lund University,Lunds universitet,Islet cell physiology,Forskargrupper vid Lunds universitet,Lund University Research Groups
-
Fan, Bo-Guang (författare)
-
- Ekelund, Mats (författare)
- Lund University,Lunds universitet,Kirurgi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Surgery (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine
-
visa fler...
-
Nordin, Gunnar (författare)
-
- Lundquist, Ingmar (författare)
- Lund University,Lunds universitet,Islet cell physiology,Forskargrupper vid Lunds universitet,Lund University Research Groups
-
visa färre...
-
(creator_code:org_t)
- 2001
- 2001
- Engelska.
-
Ingår i: American Journal of Physiology: Endocrinology and Metabolism. - 1522-1555. ; 281:1, s. 171-179
- Relaterad länk:
-
http://ajpendo.physi... (free)
-
visa fler...
-
https://lup.lub.lu.s...
-
visa färre...
Abstract
Ämnesord
Stäng
- We examined the relation between nutrient-stimulated insulin secretion and the islet lysosome acid glucan-1,4-alpha-glucosidase system in rats undergoing total parenteral nutrition (TPN). During TPN treatment, serum glucose was normal, but free fatty acids, triglycerides, and cholesterol were elevated. Islets from TPN-infused rats showed increased basal insulin release, a normal insulin response to cholinergic stimulation but a greatly impaired response when stimulated by glucose or alpha-ketoisocaproic acid. This impairment of glucose-stimulated insulin release was only slightly ameliorated by the carnitine palmitoyltransferase 1 inhibitor etomoxir. However, in parallel with the impaired insulin response to glucose, islets from TPN-infused animals displayed reduced activities of islet lysosomal enzymes including the acid glucan-1,4-alpha-glucosidase, a putative key enzyme in nutrient-stimulated insulin release. By comparison, the same lysosomal enzymes were increased in liver tissue. Furthermore, in intact control islets, the pseudotetrasaccharide acarbose, a selective inhibitor of acid alpha-glucosidehydrolases, dose dependently suppressed islet acid glucan-1,4-alpha-glucosidase and acid alpha-glucosidase activities in parallel with an inhibitory action on glucose-stimulated insulin secretion. By contrast, when incubated with intact TPN islets, acarbose had no effect on either enzyme activity or glucose-induced insulin release. Moreover, when acarbose was added directly to TPN islet homogenates, the dose-response effect on the catalytic activity of the acid alpha-glucosidehydrolases was shifted to the right compared with control homogenates. We suggest that a general dysfunction of the islet lysosomal/vacuolar system and reduced catalytic activities of acid glucan-1,4-alpha-glucosidase and acid alpha-glucosidase may be important defects behind the impairment of the transduction mechanisms for nutrient-stimulated insulin release in islets from TPN-infused rats.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
Hitta via bibliotek
Till lärosätets databas