KATP channels and insulin secretion / Frances M. Ashcroft.

Format:

Video

Author/Creator:

Ashcroft, Frances M., author.

Language:

English

Subjects (All):

Diabetes--Treatment.

Diabetes.

Potassium channels.

Physical Description:

1 online resource (1 streaming video file (50 min.)) : sound, color

Place of Publication:

London : Henry Stewart Talks Ltd, 2012.

System Details:

video file

Contents:

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

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.

Notes:

Description based on publisher supplied metadata and other sources.