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

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.

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