The Adverse Effects of Thyrotropin Absence on Pancreatic β Cell Function in Mice
Thyrotropin (TSH) is a modulator of glucose metabolism by binding to its receptor on pancreatic cells. We used thyrotropin receptor (TSHR) knockout mice (Tshr-/-) as a model of TSH deletion to study its function in pancreatic β cells. Tshr-/- mice had a similar body weight at birth compared with Tsh...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2019/9536032 |
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| Summary: | Thyrotropin (TSH) is a modulator of glucose metabolism by binding to its receptor on pancreatic cells. We used thyrotropin receptor (TSHR) knockout mice (Tshr-/-) as a model of TSH deletion to study its function in pancreatic β cells. Tshr-/- mice had a similar body weight at birth compared with Tshr+/+ mice, but grew at a significantly slower rate until adulthood with adequate thyroxine supplementation. TSH deletion led to lower fasting and postprandial blood glucose, insulin secretion impairment, and atrophy of islets in adult mice. Transcription factors and markers of pancreatic β cell maturation, Pdx1, Nkx6.1, Glut2, and insulin, together with cell proliferation marker Ki67 showed no differences at the mRNA level between the two groups. However, the Bax/Bcl-2 ratio was remarkably elevated in Tshr-/- mice at both mRNA and protein levels. We hypothesized that pancreatic cell apoptosis, rather than abnormal cell proliferation and maturation, is associated with pancreatic dysfunction and glucose intolerance in the absence of TSH modulation. |
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| ISSN: | 2314-6745 2314-6753 |