Modulation of islet G-proteins, alpha-glucosidehydrolase inhibition and insulin release stimulated by various secretagogues
(1996) In Bioscience Reports 16(1). p.23-34- Abstract
- Guanine nucleotide-binding proteins (G-proteins) are known to act as important modulators of insulin release from the islets of Langerhans. We have recently found that the deoxynojirimycin-derivative emiglitate, a recognized inhibitor of intestinal alpha-glucosidehydrolase activity, is a powerful inhibitor of glucose-induced insulin release. With the use of isolated mouse islets the present investigation was performed in a primary attempt to elucidate whether this inhibitory mechanism in some way was linked to the beta-cell G-protein system. Treatment of freshly isolated islets with pertussis toxin (PTX), which is known to inactivate the G (i)-proteins, abolished the inhibitory effect of the alpha(2)-adrenoceptor agonist clonidine on... (More)
- Guanine nucleotide-binding proteins (G-proteins) are known to act as important modulators of insulin release from the islets of Langerhans. We have recently found that the deoxynojirimycin-derivative emiglitate, a recognized inhibitor of intestinal alpha-glucosidehydrolase activity, is a powerful inhibitor of glucose-induced insulin release. With the use of isolated mouse islets the present investigation was performed in a primary attempt to elucidate whether this inhibitory mechanism in some way was linked to the beta-cell G-protein system. Treatment of freshly isolated islets with pertussis toxin (PTX), which is known to inactivate the G (i)-proteins, abolished the inhibitory effect of the alpha(2)-adrenoceptor agonist clonidine on insulin release stimulated by the phosphodiesterase inhibitor IBMX in the presence of the protein kinase C activator TPA and even changed it into an increase. Emiglitate did not display any inhibitory action on insulin release induced by these secretagogues. Similarly, clonidine-induced inhibition of glucose stimulated insulin release was reversed by PTX. However, PTX did not influence the suppressive action of emiglitate on glucose-induced insulin secretion. In contrast, the adenylate cyclase activator forskolin totally abolished the inhibitory effect of emiglitate, but not that of the glucose analogue mannoheptulose, on glucose-induced insulin release. Moreover, the stimulatory effect of forskolin and cholera toxin (CTX) (activator of G (s)-proteins) on the secretion of insulin was markedly enhanced in the presence of emiglitate. In conclusion, our results suggest that the inhibitory effect of emiglitate on glucose-induced insulin release is not directly related to the G(s)-proteins, but most likely exerted solely through the selective suppression of lysosomal aglucosidehydrolase activity, a step in between the proximal and the distal G(i)-proteins, in glucose induced stimulus-secretion mechanisms. Our data also suggests that the inhibitory action of emiglitate on glucose stimulated insulin release can be compensated for by an increased sensitivity of the cyclic AMP-protein kinase A pathway. Hence, emiglitate might indirectly elicit an increased activity of the G(s)-proteins to facilitate the secretory process. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1110695
- author
- Salehi, S Albert LU and Lundquist, Ingmar LU
- organization
- publishing date
- 1996
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Pancreatic islets, insulin secretion, pertussis toxin, cholera toxin, agr-glucosidehydrolase inhibition, insulin secretagogues
- in
- Bioscience Reports
- volume
- 16
- issue
- 1
- pages
- 23 - 34
- publisher
- Portland Press
- external identifiers
-
- pmid:8861537
- scopus:0029894259
- ISSN
- 0144-8463
- DOI
- 10.1007/BF01200998
- language
- English
- LU publication?
- yes
- id
- 04d1901c-350f-443d-a183-2f32e5120c80 (old id 1110695)
- date added to LUP
- 2016-04-01 16:42:46
- date last changed
- 2022-01-28 21:34:08
@article{04d1901c-350f-443d-a183-2f32e5120c80, abstract = {{Guanine nucleotide-binding proteins (G-proteins) are known to act as important modulators of insulin release from the islets of Langerhans. We have recently found that the deoxynojirimycin-derivative emiglitate, a recognized inhibitor of intestinal alpha-glucosidehydrolase activity, is a powerful inhibitor of glucose-induced insulin release. With the use of isolated mouse islets the present investigation was performed in a primary attempt to elucidate whether this inhibitory mechanism in some way was linked to the beta-cell G-protein system. Treatment of freshly isolated islets with pertussis toxin (PTX), which is known to inactivate the G (i)-proteins, abolished the inhibitory effect of the alpha(2)-adrenoceptor agonist clonidine on insulin release stimulated by the phosphodiesterase inhibitor IBMX in the presence of the protein kinase C activator TPA and even changed it into an increase. Emiglitate did not display any inhibitory action on insulin release induced by these secretagogues. Similarly, clonidine-induced inhibition of glucose stimulated insulin release was reversed by PTX. However, PTX did not influence the suppressive action of emiglitate on glucose-induced insulin secretion. In contrast, the adenylate cyclase activator forskolin totally abolished the inhibitory effect of emiglitate, but not that of the glucose analogue mannoheptulose, on glucose-induced insulin release. Moreover, the stimulatory effect of forskolin and cholera toxin (CTX) (activator of G (s)-proteins) on the secretion of insulin was markedly enhanced in the presence of emiglitate. In conclusion, our results suggest that the inhibitory effect of emiglitate on glucose-induced insulin release is not directly related to the G(s)-proteins, but most likely exerted solely through the selective suppression of lysosomal aglucosidehydrolase activity, a step in between the proximal and the distal G(i)-proteins, in glucose induced stimulus-secretion mechanisms. Our data also suggests that the inhibitory action of emiglitate on glucose stimulated insulin release can be compensated for by an increased sensitivity of the cyclic AMP-protein kinase A pathway. Hence, emiglitate might indirectly elicit an increased activity of the G(s)-proteins to facilitate the secretory process.}}, author = {{Salehi, S Albert and Lundquist, Ingmar}}, issn = {{0144-8463}}, keywords = {{Pancreatic islets; insulin secretion; pertussis toxin; cholera toxin; agr-glucosidehydrolase inhibition; insulin secretagogues}}, language = {{eng}}, number = {{1}}, pages = {{23--34}}, publisher = {{Portland Press}}, series = {{Bioscience Reports}}, title = {{Modulation of islet G-proteins, alpha-glucosidehydrolase inhibition and insulin release stimulated by various secretagogues}}, url = {{http://dx.doi.org/10.1007/BF01200998}}, doi = {{10.1007/BF01200998}}, volume = {{16}}, year = {{1996}}, }