Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of this study is to describe the physiological, pathophysiological and potentially therapeutic implications of bile-induced glucagon-like peptide-1 (GLP-1) secretion in human glucose homeostasis.
The investigators hypothesize that even modest increments in endogenous GLP-1 secretion will elicit important antidiabetic effects of GLP-1. To evaluate whether bile acids have such effects, the investigators plan to perform intraduodenal infusion of two different bile acids and placebo.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Colesevelam | Experimental |
| |
| Chenodeoxycholic acid | Experimental |
| |
| Colesevelam + chenodeoxycholic acid | Experimental |
| |
| Placebo | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Colesevelam | Drug | Colesevelam 3750 mg dissolved in 100 ml saline, administered in a feeding tube at time = 0. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in GLP-1 | At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes |
| Measure | Description | Time Frame |
|---|---|---|
| Change in insulin | At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes | |
| Change in C-peptide | At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes |
Not provided
Patients with type 2 diabetes
Inclusion Criteria:
Exclusion Criteria:
Healthy Volunteers
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Morten Hansen, MD | Diabetes Research Division, Department of Internal Medicine, Gentofte Hospital, University of Copenhagen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Diabetes Research Division, Department of Internal Medicine, Gentofte Hospital, University of Copenhagen | Hellerup | Copenhagen | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12419312 | Background | Maruyama T, Miyamoto Y, Nakamura T, Tamai Y, Okada H, Sugiyama E, Nakamura T, Itadani H, Tanaka K. Identification of membrane-type receptor for bile acids (M-BAR). Biochem Biophys Res Commun. 2002 Nov 15;298(5):714-9. doi: 10.1016/s0006-291x(02)02550-0. | |
| 8406158 | Background | Adrian TE, Ballantyne GH, Longo WE, Bilchik AJ, Graham S, Basson MD, Tierney RP, Modlin IM. Deoxycholate is an important releaser of peptide YY and enteroglucagon from the human colon. Gut. 1993 Sep;34(9):1219-24. doi: 10.1136/gut.34.9.1219. |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D009765 | Obesity |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000069472 | Colesevelam Hydrochloride |
| D002635 | Chenodeoxycholic Acid |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D000499 | Allylamine |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D000498 | Allyl Compounds |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Chenodeoxycholic Acid | Drug | 1.250 mg dissolved in 100 ml saline, administered in a feeding tube at time = 0. |
|
| saline | Other | 100 ml saline |
|
| Colesevelam 3750 mg + chenodeoxycholic acid 1250 mg | Drug | Colesevelam and chenodeoxycholic acid dissolved in 100 ml saline, administered in a duodenal tube at time = 0. |
|
| Change in glucagon | At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes |
| Change in glucagon-like-peptide 2 (GLP-2) | At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes |
| Change in glucose-dependent insulinotropic polypeptide (GIP) | At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes |
| Change in peptide YY (PYY) | At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes |
| Change in oxyntomodulin | At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes |
| Change in bile acids | At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes |
| Change in gastrin | At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes |
| Change in CCK | At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes |
| Change in appetite, satiety and prospective food consumption | Evaluated by Visual Analog Scale (VAS) | At baseline, and 30, 60, 90, 120 and 180 minutes |
| Change in gallbladder volume | Evaluated by ultrasound | -30, 0 (baseline), 30, 60, 120 og 180 minutes |
| Change in basal metabolic rate | Evaluated by indirect calorimetry | At -30, 60 og 150 minutes |
| Change in bile acid composition | Evaluated by duodenal aspiration | At -30, 0, 30, 60, 120 og 180 minutes |
| 15721318 | Background | Katsuma S, Hirasawa A, Tsujimoto G. Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1. Biochem Biophys Res Commun. 2005 Apr 1;329(1):386-90. doi: 10.1016/j.bbrc.2005.01.139. |
| 21521075 | Background | Rafferty EP, Wylie AR, Hand KH, Elliott CE, Grieve DJ, Green BD. Investigating the effects of physiological bile acids on GLP-1 secretion and glucose tolerance in normal and GLP-1R(-/-) mice. Biol Chem. 2011 Apr;392(6):539-46. doi: 10.1515/BC.2011.050. Epub 2011 Apr 27. |
| D004700 | Endocrine System Diseases |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000475 |
| Alkenes |
| D006839 | Hydrocarbons, Acyclic |
| D006838 | Hydrocarbons |
| D003840 | Deoxycholic Acid |
| D002793 | Cholic Acids |
| D001647 | Bile Acids and Salts |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D002757 | Cholanes |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |