Carnosine scavenging of glucolipotoxic free radicals enhances insulin secretion and glucose uptake.
The worldwide prevalence of diabetes has risen to 8.5% among adults, which represents a staggering rise in prevalence from 4.7% in 1980. Whilst some treatments work by increasing insulin secretion, over time their effectiveness decreases. We aim to increase insulin secretion by developing strategies...
| Main Authors: | , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
Nature Publishing Group
2017
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| Online Access: | https://www.nature.com/ http://hdl.handle.net/20.500.11937/93444 |
| _version_ | 1848765734940835840 |
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| author | Cripps, M.J. Hanna, K. Lavilla, C Jr Sayers, S.R. Caton, P.W. Sims, Craig De Girolamo, L. Turner, Mark |
| author_facet | Cripps, M.J. Hanna, K. Lavilla, C Jr Sayers, S.R. Caton, P.W. Sims, Craig De Girolamo, L. Turner, Mark |
| author_sort | Cripps, M.J. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | The worldwide prevalence of diabetes has risen to 8.5% among adults, which represents a staggering rise in prevalence from 4.7% in 1980. Whilst some treatments work by increasing insulin secretion, over time their effectiveness decreases. We aim to increase insulin secretion by developing strategies that work through mechanisms independent of current treatment options. Isolated CD1 mouse islets, INS-1 pancreatic β-cells, or C2C12 mouse myotubes were incubated in standard tissue culture media, or media supplemented with 28 mM glucose, 200 μM palmitic acid, and 200 μM oleic acid as a cellular model of diabetic glucolipotoxicity. Intracellular reactive species content was assayed using 2′,7′-dichlorofluorescein diacetate dye, inducible nitric oxide synthase levels determined by Western blot, 3-nitrotyrosine and 4-hydrpxnonenal both assayed by ELISA, insulin secretion quantified using ELISA or radioimmunoassay, and glucose uptake determined through 2-deoxy glucose 6 phosphate luminescence. Our data indicate that carnosine, a histidine containing dipeptide available through the diet, is an effective scavenger of each of the aforementioned reactive species. This results in doubling of insulin secretion from isolated mouse islets or INS-1 β-cells. Crucially, carnosine also reverses glucolipotoxic inhibition of insulin secretion and enhances glucose uptake into skeletal muscle cells. Thus, carnosine, or non-hydrolysable carnosine analogs, may represent a new class of therapeutic agent to fight type 2 diabetes. |
| first_indexed | 2025-11-14T11:39:58Z |
| format | Journal Article |
| id | curtin-20.500.11937-93444 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T11:39:58Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-934442023-10-25T07:34:11Z Carnosine scavenging of glucolipotoxic free radicals enhances insulin secretion and glucose uptake. Cripps, M.J. Hanna, K. Lavilla, C Jr Sayers, S.R. Caton, P.W. Sims, Craig De Girolamo, L. Turner, Mark The worldwide prevalence of diabetes has risen to 8.5% among adults, which represents a staggering rise in prevalence from 4.7% in 1980. Whilst some treatments work by increasing insulin secretion, over time their effectiveness decreases. We aim to increase insulin secretion by developing strategies that work through mechanisms independent of current treatment options. Isolated CD1 mouse islets, INS-1 pancreatic β-cells, or C2C12 mouse myotubes were incubated in standard tissue culture media, or media supplemented with 28 mM glucose, 200 μM palmitic acid, and 200 μM oleic acid as a cellular model of diabetic glucolipotoxicity. Intracellular reactive species content was assayed using 2′,7′-dichlorofluorescein diacetate dye, inducible nitric oxide synthase levels determined by Western blot, 3-nitrotyrosine and 4-hydrpxnonenal both assayed by ELISA, insulin secretion quantified using ELISA or radioimmunoassay, and glucose uptake determined through 2-deoxy glucose 6 phosphate luminescence. Our data indicate that carnosine, a histidine containing dipeptide available through the diet, is an effective scavenger of each of the aforementioned reactive species. This results in doubling of insulin secretion from isolated mouse islets or INS-1 β-cells. Crucially, carnosine also reverses glucolipotoxic inhibition of insulin secretion and enhances glucose uptake into skeletal muscle cells. Thus, carnosine, or non-hydrolysable carnosine analogs, may represent a new class of therapeutic agent to fight type 2 diabetes. 2017 Journal Article http://hdl.handle.net/20.500.11937/93444 10.1038/s41598-017-13649-w English https://www.nature.com/ http://creativecommons.org/licenses/by/4.0/ Nature Publishing Group fulltext |
| spellingShingle | Cripps, M.J. Hanna, K. Lavilla, C Jr Sayers, S.R. Caton, P.W. Sims, Craig De Girolamo, L. Turner, Mark Carnosine scavenging of glucolipotoxic free radicals enhances insulin secretion and glucose uptake. |
| title | Carnosine scavenging of glucolipotoxic free radicals enhances insulin secretion and glucose uptake. |
| title_full | Carnosine scavenging of glucolipotoxic free radicals enhances insulin secretion and glucose uptake. |
| title_fullStr | Carnosine scavenging of glucolipotoxic free radicals enhances insulin secretion and glucose uptake. |
| title_full_unstemmed | Carnosine scavenging of glucolipotoxic free radicals enhances insulin secretion and glucose uptake. |
| title_short | Carnosine scavenging of glucolipotoxic free radicals enhances insulin secretion and glucose uptake. |
| title_sort | carnosine scavenging of glucolipotoxic free radicals enhances insulin secretion and glucose uptake. |
| url | https://www.nature.com/ http://hdl.handle.net/20.500.11937/93444 |