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Incretin hormones (GLP-1 and GIP) released from the intestine in response to meal ingestion augment insulin secretion from the pancreas to help maintain glycemic control. Studies in vitro and in vivo have shown that these incretin hormones also have functional effects in other tissues independent of the insulin secretory response. Both GLP-1 and GIP stimulate insulin secretion in a glucose-dependent manner, however the glucose-dependency of their extra-pancreatic effects has not been examined in vivo. By using pancreatic clamp methodology during euglycemic and hyperglycemic conditions we will test the hypothesis that extra-pancreatic effects of GLP-1 and GIP are glucose-dependent.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control | Experimental | Saline will be coninfused during the pancreatic clamp |
|
| GIP | Experimental | GIP will be infused intravenously during the pancreatic clamp at 1.5 pmol/kg/min |
|
| GLP-1 | Experimental | GLP-1 will be infused intravenously during the pancreatic clamp at 0.5 pmol/kg/min |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Saline | Biological |
| ||
| GIP |
| Measure | Description | Time Frame |
|---|---|---|
| Glucose metabolism | Pancreatic clamp will be performed including infusion of somatostatin and replacement of basal insulin, glucagon, and growth hormone. During pancreatic clamps, euglycemia (5 mM) will be maintained via exogenous glucose infusion for the first 2-hours, followed by hyperglycemia (+5 mM) for the final 2-hours. An infusion of the stable isotope [U13C]glucose will be performed to assess glucose kinetics. Expired air will be collected for the analysis of [U13C]glucose into 13CO2. | up to 4 hours |
| Lipid metabolism | An infusion of the stable isotope [D5]glycerol will be performed to assess glycerol kinetics. | up to 4 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Endothelial function | Ultrasound Doppler will be used to examine lower and upper limb blood flow and flow-mediated dilation | Baseline, 2 hours, and 4 hours |
| Signaling | Skeletal muscle (vastus lateralis) and subcutaneous abdominal adipose biopsies will be obtained under local anaesthetic by the Bergstrom needle technique. Intracellular signalling related to glucose and lipid metabolism will be measured. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Thomas PJ Solomon, PhD | Rigshospitalet, Denmark | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rigshospitalet | Copenhagen | Capital Region | 2100 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35111398 | Derived | Solomon TPJ, Carter S, Haus JM, Karstoft K, von Holstein-Rathlou S, Nielsen MS, Gillum MP. Plasma FGF21 concentrations are regulated by glucose independently of insulin and GLP-1 in lean, healthy humans. PeerJ. 2022 Jan 19;10:e12755. doi: 10.7717/peerj.12755. eCollection 2022. |
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| ID | Term |
|---|---|
| D012965 | Sodium Chloride |
| D052216 | Glucagon-Like Peptide 1 |
| ID | Term |
|---|---|
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
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|
| GLP-1 | Biological |
|
| Baseline, 2 hours, and 4 hours |
| D017670 |
| Sodium Compounds |
| D004763 | Glucagon-Like Peptides |
| D052336 | Proglucagon |
| D005768 | Gastrointestinal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |