Incretin and KATP Channels

Effects of KATP Channel Blockers on GLP-1 and Its Analogues' Mediated Microvascular Function

This study aims to examine the involvement of KATP channels on the microvascular actions of the incretin GLP-1 and its analogues in healthy individuals and to determine whether the acute oral administration of different KATP channel blockers which are oral medications for Type 2 diabetes such as Glibenclamide and Glimepiride differentially modulate the microvascular responses in these individuals.

In addition to the glucose lowering effect, incretin based therapies have also an effect on the vascular system. Previous animal work and initial human studies suggest that incretins may be cardioprotective and act as vasodilators through opening of KATP channels.

Initial evidence suggests that beneficial vascular effects of incretin modifying agents may be nullified by the co-current treatment of the sulfonylurea (SU) drug glibenclamide. The investigators hypothesis is that the GLP-1 and SUs may have conflicting effects on the KATP channels and thus vascular function.

Interestingly the vascular actions of GLP-1 were not modified by a different treatment SUs called glimepiride, thereby raising the possibility that SUs differentially modulating the vascular actions of GLP-1 though this remains controversial.

Inclusion Criteria:

• BMI ≤ 25 kg/m2

Exclusion Criteria:

• current or past history of diabetes (HbA1C more or equal 45mmol/mol)
• history of postprandial hypoglycaemia and dumping syndrome
• established cardiovascular disease
• established cerebrovascular disease
• blood pressure ≥ 140/85 mmHg
• Raynaud's disease
• severe impairment of renalhepatic, thyroid or adrenocortical function
• current treatment with any anti-hypertensive treatment
• lipid lowering therapy or systemic steroids
• lactation, pregnancy
• established vascular disease
• bariatric surgery
• significant weight change within the last 3 months