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Printable Handouts
Navigable Slide Index
- Introduction
- KATP channels and insulin secretion (1)
- Structure of the KATP channel
- Expression of Kir6.2 and SUR1
- KATP channels link metabolism to electrical activity
- Functional roles of the KATP channel
- KATP channels are regulated by metabolism (1)
- KATP channels are regulated by metabolism (2)
- Metabolic regulation involves both subunits
- Molecular model of the Kir6.2 tetramer
- KATP channels are inhibited by ATP
- Mg-nucleotides open channels via SUR NBDs (1)
- Mg-nucleotides open channels via SUR NBDs (2)
- Mg-nucleotides open channels via SUR NBDs (3)
- SUR1 modulates Kir6.2
- ATP blocks channels by binding to Kir6.2
- ATP sensitivity lowers in open-cell configuration
- KATP channels are activated by PIP2
- KATP channels and insulin secretion (2)
- Insulin is important in blood glucose homeostasis
- Insulin is not a cure
- Several types of diabetes
- KATP channels and insulin secretion (2)
- Therapeutic drugs regulate KATP channels
- KATP channels and insulin secretion (3)
- Familial hyperinsulinaemia
- The KATP current is reduced in hyperinsulinism
- Mechanism of action of HI mutations
- SUR1 HI mutations change membrane expression
- Some HI mutations are not activated by MgATP/ADP
- Location of HI mutations in Kir6.2 model
- Some HI mutations impair activation by PIP2
- KATP channels and insulin secretion (4)
- Neonatal diabetes
- Location of ND mutations in Kir6.2 model (1)
- Location of ND mutations in Kir6.2 model (2)
- Increased KATP current in neonatal diabetes
- Increased current in ND via different mechanisms
- Mutations in the ATP-binding site
- R50P is blocked less by ATP
- Mutations that alter gating and ATP sensitivity (1)
- I296L is less sensitive to ATP
- Gating mutations increase intrinsic Po
- I296 may form a cytosolic gate
- Disease severity-KATP current correlation (Kir6.2)
- Location of ND mutations in SUR1
- Mutations that alters gating and ATP sensitivity (2)
- Mutations altering MgATP hydrolysis (1)
- Mutations altering MgATP hydrolysis (2)
- Disease severity-KATP current correlation (SUR1)
- KATP channels and diabetes
- Implications for therapy
- Sulphonylureas close KATP channels (1)
- Sulphonylureas close most mutant KATP channels
- Glucose control is improved on sulphonylureas
- Oral glucose is more effective than IV glucose
- Incretin response restored after treatment with SU
- Can SU improve extra-pancreatic symptoms?
- Glibenclamide enhances brain blood flow
- Summary-KATP mutations and ND
- NOT lost in translation
- Kir6.2 mutations relevant to type 2 diabetes
- Further reading
- Acknowledgements
Topics Covered
- KATP channels and insulin secretion
- Structure of the KATP channel
- Functional roles
- Regulation by metabolism, nucleotides and lipids
- Overview of insulin secretion and diabetes
- Effects of loss-of-function KATP channel mutations
- Effects of gain-of-function KATP channel mutations
- Implications for the treatment of neonatal diabetes
Links
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Talk Citation
Ashcroft, F.M. (2012, July 3). KATP channels and insulin secretion [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 6, 2024, from https://doi.org/10.69645/SKPB4715.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Frances Mary Ashcroft has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.