Amylin and Glucagon-Like Peptide-1 (GLP-1): Influence on Gastric Emptying, Appetite and Food Intake in Humans

Study Overview
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Brief Summary
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The aim of this proposal is to dissect the mechanisms controlling gastric emptying, appetite and food intake in humans, and to obtain new knowledge to fight obesity on a pharmacological basis.

Detailed Description
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The objective of the present study is to elucidate the mechanisms behind the effects of glucagon-like peptide-1 (GLP-1) on gastric emptying, appetite and food intake. The first GLP-1 based anti-diabetic therapy was approved by the FDA in 2005 and is now on the market in the United States. The strong glucose-dependent insulinotropic property of GLP-1 is a highly attractive feature in the pursue of optimal glycaemic control in type 2 diabetes. Moreover, the potential of GLP-1 to reduce gastric emptying, appetite and food intake makes it an attractive tool in the fight against obesity, a pandemic condition that often leads to type 2 diabetes, and several companies are developing weight lowering drugs based on GLP-1. Interestingly, another peptide, amylin, exerts very similar effects on gastric emptying, appetite and food intake in humans. Amylin is found in insulin-rich granules in pancreatic beta-cells and is co-secreted with insulin upon insulinotropic stimuli. Currently, it is not known whether the inhibiting effects of GLP-1 on gastric emptying, appetite and food intake are directly mediated by GLP-1, or if the effects are secondary to the robust insulin responses, and thereby amylin responses, elicited by GLP-1. The objective of the present study is therefore to further elucidate the mechanisms of these effects in order to strengthen the development of anti-diabetic drugs with potential weight lowering capabilities.

Official Title
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Amylin and GLP-1: Influence on Gastric Emptying, Appetite and Food Intake in Humans.

Conditions
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Diabetes

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with type 1 diabetes Informed oral and written consent Caucasians over the age of 18 years with type 1 diabetes (diagnosed according to the criteria of WHO) receiving long acting insulin C-peptide negative glucagon test Normal blood haemoglobin concentration Healthy control subjects Informed oral and written consent Caucasians over the age of 18 years Normal 75 g- oral glucose tolerance test (OGTT) according to the criteria of WHO Negative islet cell autoantibodies (ICA) and GAD-65 autoantibodies No first-degree relatives with diabetes Normal blood haemoglobin concentration Exclusion Criteria: Patients with type 1 diabetes Residual beta-cell function (evaluated with glucagon test) Impaired hepatic function (aspartate aminotransferase (ASAT) and/or alanine aminotransferase (ALAT) > 2 times upper normal limit) Diabetic nephropathy (serum-creatinine > 130 µM and/or albuminuria) Diabetic neuropathy Proliferative diabetic retinopathy Pregnancy, breastfeeding or intention of becoming pregnant or judged to be using inadequate contraceptive measures Healthy control subjects Impaired hepatic function (ASAT or ALAT > 2 times upper normal limit) Impaired renal function (serum-creatinine > 130 μM and/or albuminuria) First-degree relatives with diabetes Pregnancy, breastfeeding or intention of becoming pregnant or judged to be using inadequate contraceptive measures

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amylin, GLP-1, gastric emptying, appetite and food intake