Cited by 47Pancreatic function and diabetesEndoplasmic Reticulum Stress and DiseaseDiabetes and associated disorders

Inhibitory Effects of Streptozotocin, Tumor Necrosis Factor-α, and Interleukin-1β on Glucokinase Activity in Pancreatic Islets and Gene Expression of GLUT2 and Glucokinase

Park, Chun, Kim, Jeong-Ran, Shim, Jae-Kyoung, Kang, Bong-Seok, Park, Young-Guk, Nam, Kyung-Soo, Lee, Young-Choon, Kim, Cheorl-Ho·1999·Archives of Biochemistry and Biophysics

Abstract

Treatment of streptozotocin (ST), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) resulted in destroying insulin-secreting beta-cells of pancreatic islets and impairment of islet glucose oxidation and glucose-induced insulin secretion. IL-1beta and TNF-alpha inhibited insulin release and glucose utilization and oxidation. It was shown that the inhibitory effects of ST, IL-1beta, and TNF-alpha were due to impaired glucokinase activity. Glucokinase activity was severely impaired by ST, IL-1beta, and TNF-alpha treatments, as confirmed by assaying enzymes and nucleotides associated with glycolysis and glucose oxidation. On the other hand, nitric oxide was a factor of the deleterious effects of IL-1beta, TNF-alpha, and ST on pancreatic islets. Incubation of mouse pancreatic islets with ST at various concentrations of impairing insulin secretion resulted in generation of nitrite, stimulation of islet guanylyl cyclase and accumulation of cGMP, and inhibition of pancreatic islet mitochondrial aconitase activity to degree similar to those raised by IL-1beta and TNF-alpha. When the effects of IL-1beta and TNF-alpha on the gene expression of pancreatic GLUT2 and glucokinase were examined, the level of GLUT2 and glucokinase mRNA in pancreatic islets was significantly decreased. This suggested that IL-1beta and TNF-alpha downregulate gene expression of GLUT2 and glucokinase in pancreatic beta-cells.

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Crossref · 10.1006/abbi.1998.1004

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  • The proinflammatory cytokines, such as IL-1β, IFN-γ, and TNF-α, inhibit glucose-stimulated insulin secretion and proliferation of beta-cells.

    “The proinflammatory cytokines, such as interleukin-1 beta (IL-1β), interferon gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α), inhibit glucose-stimulated insulin secretion and proliferation of beta-cells [40–42].”

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Authors
Park, C., Kim, J.-R., Shim, J.-K., Kang, B.-S., Park, Y.-G., Nam, K.-S., Lee, Y.-C., & Kim, C.-H.
Affiliations
  • Dongguk University (KR)
  • Kyung Hee University (KR)
  • Dong-A University (KR)
Corresponding author
Kim, Cheorl-Ho
Venue
Archives of Biochemistry and Biophysics
Publisher
Elsevier BV
Published
1999-02
Volume
362
Issue
2
Pages
217-224
ISSN
0003-9861 (ISSN-L)
OpenAlex
W2014545958
Cited by
47
References
46
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2022: 1 · 2021: 1 · 2019: 4 · 2018: 3 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 2
FWCI
3.16
Type
journal article
Language
en
Open access
closed
Locations
  • Archives of Biochemistry and Biophysics (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Research Foundation of Korea
  • Ministry of Education, Kenya
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Keywords
streptozotocin, TNF-α, IL-1β, glucokinase, GLUT2, pancreatic islets, beta-cell dysfunction, insulin secretion, glucose oxidation, nitric oxide, cyclic GMP, guanylate cyclase, mitochondrial aconitase, gene downregulation, insulitis
MeSH terms
Insulin Secretion, Aconitate Hydratase, Adenine Nucleotides, Animals, Glucokinase, Glucose, Glucose-6-Phosphatase, Cyclic GMP, Hexokinase, Insulin, Interleukin-1, Islets of Langerhans, Male, Mitochondria, Monosaccharide Transport Proteins, Nitric Oxide, Nitroprusside, Pancreas, Pyruvate Dehydrogenase Complex, Streptozocin, Tumor Necrosis Factor-alpha, Gene Expression, Glucose Transporter Type 2, Mice

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