Related Experiment Video
Updated: Aug 25, 2026
Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test (OGTT) and Insulin Tolerance Test (ITT)
Published on: January 7, 2018
[Preventive effects of pioglitazone on diabetes and relevant mechanisms, experimental study on non-obese diabetic
Jian-hao Pei1, Zhi-guang Zhou, Jian-hua Luo
1Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha 410011, China.
Objective:
To explore the effects of pioglitazone on insulitis and diabetes and relevant mechanism.
Methods:
Seventy-three female non-obese diabetic (NOD)/Lt mice aged 4 weeks were randomly divided into 3 groups, control group (n = 25, fed with regular diet), low dosage pioglitazone group (n = 23, pioglitazone of the concentration of 0.01% was added into the feed) and high dosage pioglitazone group (n = 25, pioglitazone of the concentration of 0.04% was added into the feed). The mice were killed when diabetes developed or they reached the age of 30 weeks. The body weight and amount of food intake were measured every week and the amount of drug intake was calculated. Urine glucose was checked weekly from week 10 to week 30. When urine glucose was positive and relevant symptoms appeared, blood glucose was measured. The criterion of diagnosis of diabetes was the consecutive blood glucose level > or = 16.7 mmol/L for 2 times. At the 12th week 4-7 mice from the 3 groups respectively were killed and their pancreases were removed to be scored on insulitis by HE staining, the spleen cells were cultured. The IL-4 and IFN-r levels in serum and supernatants of spleen cell cultures were measured by ELISA. The pancreatic IFN-r mRNA level was tested using RT-PCR method.
Results:
(1) At the age of 30 weeks, the diabetes incidence rates was 80% (20/25) in the control group, 60.9% (14/23) in the low dose group, and 60% (15/25) in the high dose group (P > 0.05). At the following time points the diabetes incidence rates of the 2 treated groups were lower than that of the control group (all P < 0.05): (1) 0% in the low dose group vs 16%: of the control group at the age of 100 days, and 39% vs 68% at the age of 185 days; and (2) 0% in the high dose group vs 16% in the control group at the age of 110 days, 4% vs 24% at the age of 120 days, and 12%vs 36% at the age of 135 days. (2) There was no difference in insulitis scores between the control group and low dose or high dose groups at the age of 12 weeks (1.99 +/- 0.75 vs 1.01 +/- 0.68 and 1.19 +/- 0.84, both P > 0.05), however, the score of the combined pioglitazone group (low dose group + high dos group) was significantly higher than that of the control group (1.12 +/- 0.75 vs 1.99 +/- 0.75, P < 0.05). (3) There was no differences in the IL-4/IFN-r ratios in serum and splenocyte culture supernatant and pancreatic IFN-r mRNA levels among the three groups (all P > 0.05).
Conclusion:
Pioglitazone, to some extent, lessens the insulitis severity and delays the diabetes onset. Its mechanism may be unrelated to immune deviation of Th1 to a Th2.
Insights
Pioglitazone treatment in non-obese diabetic mice showed a trend towards reduced diabetes incidence and insulitis severity. The study suggests its mechanism is not related to Th1/Th2 immune deviation.
Area of Science:
- Immunology
- Endocrinology
- Pharmacology
Background:
- Insulitis, an autoimmune process targeting pancreatic beta cells, is a hallmark of type 1 diabetes.
- Pioglitazone, a thiazolidinedione, is known for its insulin-sensitizing effects in type 2 diabetes.
Purpose of the Study:
- To investigate the therapeutic effects of pioglitazone on insulitis and diabetes development in a mouse model.
- To explore the underlying mechanisms, particularly immune responses, influenced by pioglitazone.
Main Methods:
- Non-obese diabetic (NOD)/Lt mice were administered varying doses of pioglitazone or a control diet.
- Diabetes incidence, insulitis scores, and immune markers (IL-4, IFN-γ) were assessed.
- Pancreatic tissue and spleen cells were analyzed for histological and molecular changes.
Main Results:
- Pioglitazone treatment showed a trend towards reduced diabetes incidence compared to controls, particularly at later time points.
- While insulitis scores were not significantly different at 12 weeks, a combined analysis suggested a potential reduction in severity.
- No significant differences were observed in IL-4/IFN-γ ratios or pancreatic IFN-γ mRNA levels, indicating the mechanism is likely independent of Th1/Th2 deviation.
Conclusions:
- Pioglitazone demonstrates a potential to ameliorate insulitis and delay diabetes onset in NOD mice.
- The observed effects appear to be independent of a shift in the balance between Th1 and Th2 immune responses.
Related Concept Videos
01:26Oral Hypoglycemic Agents: Biguanides and Glitazones
01:23Dipeptidyl Peptidase 4 Inhibitors
01:24Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...