We hypothesize that membrane-residing gangliosides are elevated in obese insulin resistant subjects and correlate to peripheral insulin resistance. Furthermore, we hypothesize that the perturbation of the insulin signaling cascade by elevated…
ID
Bron
Verkorte titel
Aandoening
Diabetes, obesity, insulin resistance,
Ondersteuning
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
- Peripheral glucose uptake (Rd)<br>
- Ganglisosides concentration in muscle and adipose tissue
Achtergrond van het onderzoek
Gangliosides reside within the plasma membrane and are able to modulate insulin signaling at the level of the insulin receptor. The most abundant ganglioside is GM3. Recently, we and others have shown in rats that pharmacologically reducing GM2 and GM3 levels results in amelioration of high fat diet induced insulin resistance. In this study we want to explore if gangliosides are elevated in muscle and adipose tissue of obese subjects inslin resistant subjects compared to matched healthy controls.
Doel van het onderzoek
We hypothesize that membrane-residing gangliosides are elevated in obese insulin resistant subjects and correlate to peripheral insulin resistance.
Furthermore, we hypothesize that the perturbation of the insulin signaling cascade by elevated gangliosides is caused by a reduced phosphorylation of the insulin receptor.
Onderzoeksopzet
N/A
Onderzoeksproduct en/of interventie
None:
This is a comparitive study; 10 obese men mached for gender and age with 10 lean men.
Publiek
F5-162 Endocrinology and Metabolism
M. Brands
Meibergdreef 9
Amsterdam 1100 DD
The Netherlands
+31 (0)20 5662663
m.brands@amc.uva.nl
Wetenschappelijk
F5-162 Endocrinology and Metabolism
M. Brands
Meibergdreef 9
Amsterdam 1100 DD
The Netherlands
+31 (0)20 5662663
m.brands@amc.uva.nl
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
Inclusion criteria for all participants
1. Written informed consent
2. Caucasian
3. Able to keep a normal day and night rhythm during the study period (i.e. no shift work)
4. Stable weight for at least 3 months
5. Age 20-55 years
Inclusion criteria for healthy volunteers:
1. 20 ¡Ü BMI ¡Ü 25 kg/m2
2. Fasting glucose level of < 5.6 mmol/L, in addition to a glucose level of < 7.8 mmol/L at 2 hours after intake of 75 g glucose (OGTT).
Inclusion criteria for obese subjects:
1. BMI >30 kg/m2
2. Fasting glucose level of < 7 mmol/L, in addition to a glucose level of < 11.0 mmol/L at 2 hours after intake of 75 g glucose (OGTT).
3. HOMA IR > 2.7
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
Exclusion criteria for all participants:
1. Participation in an investigational drug trial within 90 days prior to our study
2. history of or current abuse of drugs or alcohol (>14 U/week)
3. Smoking
4. Vigorous physical activity
5. Family history of DM II
6. Familial dyslipidemia
7. Any medical condition except hypertension and dyslipidemia in the obese group
8. Use of any medication except for anti-hypertensives, excluding ACE-inhibitors/AII-antagonists.
Opzet
Deelname
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