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
Elevations of blood glucose and lipid are thought to be deleterious to the insulin secretory function of the pancreas. This is known as glucolipotoxicity. However, few studies have examined this in detail. This investigation will examine pancreatic insulin secretory function in physiological models of glucolipotoxicity such as obese and type 2 diabetic individuals. Furthermore, healthy subjects will undergo 24 hour infusion of glucose or Intralipid to induce experimental models of glucolipotoxicity. Insulin secretion in response to intravenous infusions of glucose, GLP-1, GIP, and arginine and in response to meal ingestion, will be examined. the investigators hypothesize that experimental glucolipotoxicity will impairs pancreatic insulin secretory function to levels akin to that seen in type 2 diabetics.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Glucotoxicity Trial | Experimental | Insulin secretion will be assessed using a hyperglycemic clamp combined with GLP-1, GIP, and arginine infusions. The clamp will be performed before and after 24 hours of bed rest, isocaloric meal feeding, and experimental elevation of blood glucose. |
|
| Control Trial | No Intervention | Insulin secretion will be assessed using a hyperglycemic clamp combined with GLP-1, GIP, and arginine infusions. The clamp will be performed before and after 24 hours of bed rest and isocaloric meal feeding. | |
| Lipotoxicity Trial | Experimental | Insulin secretion will be assessed using a hyperglycemic clamp combined with GLP-1, GIP, and arginine infusions. The clamp will be performed before and after 24 hours of bed rest, isocaloric meal feeding, and experimental elevation of blood free fatty acids. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Glucotoxicity | Procedure | Glucose will be infused intravenously for a 24 hour period to raise blood glucose concentrations 5 mM above basal. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Insulin Secretion | Insulin secretion will be assessed in response to intravenous infusions of glucose, GLP-1, GIP, and arginine, and in response to meal ingestion. | 24 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Insulin Sensitivity | Glucose kinetics will be assesed using [6,6-2H2]glucose. Rate of glucose disappearance during glucose infusion will be quantified per unit of plasma insulin to derive an estimate of insulin sensitivity. | 24 hours |
| Plasma Cytokines (IL-6, TNF, IL-1beta, IL-1ra) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Thomas P Solomon, Ph.D. | Rigshospitalet, Denmark | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre of Inflammation and Metabolism, Rigshospitalet | Copenhagen | 2100 | Denmark |
Not provided
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Lipotoxicity | Procedure | Intralipid and heparin will be infused intravenously for a 24 hour period to raise blood free fatty acid concentrations to approximately 1 mM. |
|
Cytokines will be measured in plasma: IL-6, TNF-alpha, IL-1beta, IL-1 receptor antagonist, IL-8, IL-10, Interferon gamma. Peripheral blood mononuclear cells will be isolated. |
| 24 hours |