Alterations in β-cell calcium dynamics and efficacy outweigh islet mass adaptation in compensation of insulin resistance and prediabetes onset
| Autor: | Stephan René Jahn, Chunguang Chen, Ingo Uphues, Christian M. Cohrs, Helena Chmelova, Julie A. Chouinard, Stephan Speier, Julia Stertmann |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
geography medicine.medical_specialty geography.geographical_feature_category Endocrinology Diabetes and Metabolism Insulin medicine.medical_treatment Type 2 diabetes Biology Islet medicine.disease Insulin oscillation 03 medical and health sciences 030104 developmental biology Insulin resistance Endocrinology Internal medicine Diabetes mellitus Internal Medicine medicine Glucose homeostasis Prediabetes |
| Zdroj: | Diabetes 65, 2676-2685 (2016) |
| Popis: | Emerging insulin resistance is normally compensated by increased insulin production of pancreatic β-cells, thereby maintaining normoglycemia. However, it is unclear whether this is achieved by adaption of β-cell function, mass, or both. Most importantly it is still unknown which of these adaptive mechanisms fail when type 2 diabetes develops. We performed longitudinal in vivo imaging of β-cell calcium dynamics and islet mass of transplanted islets of Langerhans throughout diet-induced progression from normal glucose homeostasis, over compensation of insulin resistance to pre-diabetes. The results show that compensation of insulin resistance is predominated by alterations of β-cell function, while islet mass only gradually expands. Hereby, functional adaptation is mediated by increased calcium efficacy, which involves Epac signaling. Prior to prediabetes, β-cell function displays decreased stimulated calcium dynamics, whereas islet mass continues to increase through prediabetes onset. Thus, our data reveal a predominant role of islet function with distinct contributions of triggering and amplifying pathway in the in vivo processes preceding diabetes onset. These findings support protection and recovery of β-cell function as primary goal for prevention and treatment of diabetes and provide insight into potential therapeutic targets. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|