Incretin and KATP Channels

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Healthy Subjects

Intervention / Treatment
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* Other: Intradermal injections of GLP-1 and its analogues


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glimepiride<br>4mg of Glimepiride once only before vascular testing and intradermal injections of GLP-1 and its analogues | Other: Intradermal injections of GLP-1 and its analogues<br>* native GLP-1,Exenatide (Byetta)and Liraglutide (Victoza) will be microinjected at the same visit in no particular order in all study arms<br>* Other names: and Liraglutide (Victoza);|
| Placebo Comparator: Placebo tablet<br>Placebo tablet is given in the morning of the intradermal injections of GLP-1 and its analogues | Other: Intradermal injections of GLP-1 and its analogues<br>* native GLP-1,Exenatide (Byetta)and Liraglutide (Victoza) will be microinjected at the same visit in no particular order in all study arms<br>* Other names: and Liraglutide (Victoza);|
| Active Comparator: Glyburide<br>10mg of Glyburide before study visit and intradermal injections of GLP-1 and its analogues | Other: Intradermal injections of GLP-1 and its analogues<br>* native GLP-1,Exenatide (Byetta)and Liraglutide (Victoza) will be microinjected at the same visit in no particular order in all study arms<br>* Other names: and Liraglutide (Victoza);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in skin blood flow to GLP-1 and its analogues | Skin blood flow will be assessed before and after microinjection of GLP-1 or its analogues and the injection site monitored and compared to sites injected with placebo | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Incretins, KATP channels, intradermal injection