Inhibitory Effects of Streptozotocin, Tumor Necrosis Factor-α, and Interleukin-1β on Glucokinase Activity in Pancreatic Islets and Gene Expression of GLUT2 and Glucokinase
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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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].”
From Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control (2016) · cites this paper as [41]
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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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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