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The Insulin Sensitizer KBP-336 Prevents Diabetes-Induced Cognitive decline in ZDF Rats
A T Larsen1, K E Mohamed, E A Petersen
1Anna Thorsø Larsen, Nordic Bioscience A/S, Herlev Hovedgade 207, DK-2730, Herlev, Denmark. Tel: +45 44525252.
Background And Objectives:
Diabetes and especially insulin resistance are associated with an increased risk of developing cognitive dysfunction, making anti-diabetic drugs an interesting therapeutic option for the treatment of neurodegenerative disorders. Dual amylin and calcitonin receptor agonists (DACRAs) elicit beneficial effects on glycemic control and insulin sensitivity. However, whether DACRAs affect cognition is unknown.
Design And Intervention:
Zucker Diabetic Fatty rats were treated with either the DACRA KBP-336 (4.5 nmol/kg Q3D), the amylin analog AM1213 (25 nmol/kg QD), or vehicle for 18 weeks. Further, the efficacy of a late KBP-336 intervention was evaluated by including a group starting treatment on day 30. Glucose control and tolerance were evaluated throughout the study and spatial learning and memory were evaluated by Morris Water Maze after 17 weeks of treatment.
Results:
When evaluating spatial learning, rats receiving KBP-336 throughout the study performed significantly better than AM1213, vehicle, and late intervention KBP-336. Both KBP-336 and AM1213 treatments improved spatial memory compared to the vehicle. The overall performance in the cognitive tests was reflected in the treatment efficacy on glycemic control, where KBP-336 was superior to AM1213.
Conclusion:
In summary, the DACRA KBP-336 ameliorates diabetes-induced spatial learning and memory impairment in diabetic rats. Further, KBP-336 improves long-term glycemic control superior to the amylin analog AM1213. Taken together, KBP-336 is, due to its anti-diabetic and insulin-sensitizing properties, a promising candidate for the treatment of cognitive impairments.
Insights
Dual amylin and calcitonin receptor agonists (DACRAs) show promise for treating cognitive dysfunction. The DACRA KBP-336 improved spatial learning and memory in diabetic rats, outperforming an amylin analog.
Area of Science:
- Neuroscience
- Endocrinology
- Pharmacology
Background:
- Insulin resistance and diabetes are linked to cognitive dysfunction.
- Anti-diabetic drugs are potential treatments for neurodegenerative disorders.
- Dual amylin and calcitonin receptor agonists (DACRAs) improve glycemic control and insulin sensitivity.
Purpose of the Study:
- To investigate the effects of DACRAs on cognitive function in a diabetic rat model.
- To compare the efficacy of a specific DACRA (KBP-336) with an amylin analog (AM1213) on cognitive performance and glycemic control.
Main Methods:
- Zucker Diabetic Fatty rats were treated with KBP-336, AM1213, or vehicle for 18 weeks.
- A late intervention group received KBP-336 starting on day 30.
- Spatial learning and memory were assessed using the Morris Water Maze.
Main Results:
- KBP-336 treatment significantly improved spatial learning compared to AM1213, vehicle, and late intervention.
- Both KBP-336 and AM1213 enhanced spatial memory over vehicle treatment.
- KBP-336 demonstrated superior glycemic control compared to AM1213.
Conclusions:
- The DACRA KBP-336 ameliorates diabetes-induced spatial learning and memory deficits in diabetic rats.
- KBP-336 exhibits superior long-term glycemic control compared to the amylin analog AM1213.
- KBP-336 is a promising therapeutic candidate for cognitive impairments due to its anti-diabetic and insulin-sensitizing effects.
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