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 human brain is an insulin sensitive organ. Brain insulin action modulates peripheral insulin sensitivity in young lean men. As a underlying mechanism, the investigators previously detected suppression of endogenous glucose production and stimulation of glucose disappearance to peripheral tissue in response to brain insulin delivery by nasal spray. Whether this holds true in young woman is unknown, since differences in brain insulin response between sexes have been reported. The investigators will address this question by combining the delivery of insulin to the brain as nasal spray with hyperinsulinemic euglycemic clamp experiments in natural cycling women.
In the planned randomized, placebo controlled cross-over study, female participants will undergo four hyperinsulinemic euglycemic experiments with tracer dilution, two in the first phase and two in the second phase of their menstrual cycle. On one of the study days per menstrual phase, subjects will receive intranasal insulin administration, on the other placebo spray. The protocol has been successfully applied previously in men. Based on the results of this trial, the investigators calculated a required sample size of N=10 for the planned study in women.
These experiments will help to better understand the role of brain insulin action in a broader sense. The results can be the basis for larger clinical trials that address the sex-specific impact of brain insulin resistance for glucose metabolism and diabetes risk.
"Effect of central insulin administration on whole-body insulin sensitivity in women" The human brain is an insulin sensitive organ. Brain insulin action modulates peripheral insulin sensitivity in young lean men. As a underlying mechanism, the investigators previously detected suppression of endogenous glucose production and stimulation of glucose disappearance to peripheral tissue in response to brain insulin delivery by nasal spray. Whether this holds true in young woman is unknown, since differences in brain insulin response between sexes have been reported. The investigators will address this question by combining the delivery of insulin to the brain as nasal spray with hyperinsulinemic euglycemic clamp experiments in natural cycling women.
In the planned randomized, placebo controlled cross-over study, female participants will undergo four hyperinsulinemic euglycemic experiments with tracer dilution, two in the first phase and two in the second phase of their menstrual cycle. On one of the study days per menstrual phase, subjects will receive intranasal insulin administration, on the other placebo spray. The protocol has been successfully applied previously in men. Based on the results of this trial, the investigators calculated a required sample size of N=10 for the planned study in women.
These experiments will help to better understand the role of brain insulin action in a broader sense. The results can be the basis for larger clinical trials that address the sex-specific impact of brain insulin resistance for glucose metabolism and diabetes risk.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Insulin nasal spray | Active Comparator | 160 Units of human insulin as nasal spray |
|
| Placebo nasal spray | Placebo Comparator | Nasal spray containing placebo solution |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| intranasal insulin | Drug | application of 160 units human insulin |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change in the peripheral insulin sensitivity | Effect of nasal insulin versus placebo on peripheral insulin sensitivity assessed by euglycemic hyperinsulinemic clamp. | 60-90 minutes and 150-210 minutes during euglycemic clamp |
| Measure | Description | Time Frame |
|---|---|---|
| Correlation with autonomous nervous system activity | Correlation of the change in peripheral insulin sensitivity by central insulin action with the simultaneous change of the autonomous nervous system (measured by heart rate variability). | 70-80 minutes and 190-200 minutes during euglycemic clamp |
| Differential effects dependent on female sexual hormones |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Tuebingen, Department of Internal Medicine IV | Tübingen | 72076 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37735274 | Derived | Hummel J, Benkendorff C, Fritsche L, Prystupa K, Vosseler A, Gancheva S, Trenkamp S, Birkenfeld AL, Preissl H, Roden M, Haring HU, Fritsche A, Peter A, Wagner R, Kullmann S, Heni M. Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase. Nat Metab. 2023 Sep;5(9):1475-1482. doi: 10.1038/s42255-023-00869-w. Epub 2023 Sep 21. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo spray |
| Drug |
nasal spray containing placebo solution |
|
Correlation of the change in peripheral insulin sensitivity by central insulin action dependent on the time point in menstrual cycle |
| 60-90 minutes and 150-210 minutes during euglycemic clamp |
| Effect of menstrual cycle on insulin sensitivity before spray application | Will be measured by hyperinsulinemic euglycemic clamp | 60-90minutes |
| Effect of menstrual cycle on brain insulin sensitivity | Brain insulin sensitivity will be assessed by functional magnetic resonance imaging combined with intranasal insulin administration during the follicular and the luteal phase of the menstrual cycle | 60-90 minutes |
| Effect of menstrual cycle on processing of food cues in the brain | Processing of food cues in the brain will be assessed by functional magnetic resonance imaging during the follicular and the luteal phase of the menstrual cycle | 20 minutes |