TPN-evoked dysfunction of islet lysosomal activity mediates impairment of glucose-stimulated insulin release
Salehi, S Albert LU
; Fan, Bo-Guang
; Ekelund, Mats
LU
; Nordin, Gunnar
and Lundquist, Ingmar
LU
(2001)
In American Journal of Physiology: Endocrinology and Metabolism
281(1).
p.171-179
- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1122276
- author
- Salehi, S Albert
LU
; Fan, Bo-Guang
; Ekelund, Mats
LU
; Nordin, Gunnar
and Lundquist, Ingmar
LU
- organization
- publishing date
- 2001
- type
- Contribution to journal
- publication status
- published
- subject
- in
- American Journal of Physiology: Endocrinology and Metabolism
- volume
- 281
- issue
- 1
- pages
- 171 - 179
- publisher
- American Physiological Society
- external identifiers
-
- pmid:11404235
- scopus:0034807945
- ISSN
- 1522-1555
- language
- English
- LU publication?
- yes
- id
- 230bae66-12c1-4ba5-9e70-c880a970690e (old id 1122276)
- alternative location
- http://ajpendo.physiology.org/cgi/reprint/281/1/E171.pdf
- date added to LUP
- 2016-04-04 09:04:41
- date last changed
- 2022-01-29 08:06:41
@article{230bae66-12c1-4ba5-9e70-c880a970690e,
abstract = {{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.}},
author = {{Salehi, S Albert and Fan, Bo-Guang and Ekelund, Mats and Nordin, Gunnar and Lundquist, Ingmar}},
issn = {{1522-1555}},
language = {{eng}},
number = {{1}},
pages = {{171--179}},
publisher = {{American Physiological Society}},
series = {{American Journal of Physiology: Endocrinology and Metabolism}},
title = {{TPN-evoked dysfunction of islet lysosomal activity mediates impairment of glucose-stimulated insulin release}},
url = {{http://ajpendo.physiology.org/cgi/reprint/281/1/E171.pdf}},
volume = {{281}},
year = {{2001}},
}