Hi all
I am working in my PhD, and I have a problem. When comparing the data from my control group with the data of a group treated with resveratrol I find that:
- No differences are observed among the groups (control and resveratrol) concerning insulin levels and HOMA-IR.
- However, the resveratrol administration produced an improvement in the glycaemia curves after glucose tolerance test (the glucose was injected intraperitoneally) and also the basal glucemia was lower in the treated group.
After reading different papers/reviews I am not able to find an explanation/justification for this results.
Any suggestion-advice would be very appreciated
Thanks in advance
Iñaki
You do not say which species you are studying nor whether you have statistical power to say you saw no difference. However, post prandial measures are usually more revealing than basal levels.
Hi Christine
First of all thank you. The study is made in rats (Wistar). The differences observed in the glucose tolerance test (after intra peritoneal injection of glucose, 2gr/kg body weight) occur only after 30 and 60 minutes after glucose administration. At minutes 90 and 120 no difference were observed among the groups.
Could be that resveratrol makes the initial response to glucose administration more efficient (or more sensitive towards insulin effects) but with no enough power to produce differences along all the glucose tolerance test (I mean, during the 120 minutes that the test lasts)?
When was RSV administered in relation to glucose time wise and how was it administered?
Hi Thomas
RSV was administered daily in the food. These rats, were fasted the night before the GTT. At fasting state, and after measurement of basal glucose, the glucose was injected.
Given the short half life of RSV my best guess would be that you are seeing an acute effect of RSV that is weaning of after the overnight fast. It is just a guess since my experience is related to chronic effects of RSV. Best of luck.
Maybe look into glucose transporter expression int the groups? After fasting: Increased insulin receptor affinity in RSV group beyond that of the other groups which is then downregulated after glucose administration (either the number of receptors or the affinity of the receptor)?
Again...just speculating.
Inaki how long was the fasting? Overnight fasting, according to my experience can complex glucose measuring and in some cases rats with severe diabetes may appear "normal" in the morning. Choose a 4-hour fasting in the morning (9-13:00) and check again your curves. That's my opinion, since I faced an almost similar problem 3 years ago at the beginning of my PhD.
Hi Ioannis
The fasting was overnight. Thanks for sharing your experience
Could this be related to an effect on the release of insulin by the pancreas?
Even when glucose tolerance is improved because the pancreas can secrete insulin more readily, you may see no change in whole body insulin resistance by HOMA.
It could be explained by the insulin sensitizer feature of resveratrol. In basal condition glycaemia and insulineamia are not affected but once a functional test is performed the body low glycaemia of an higher degree with the very same amount of insulin. i would reccomend to search for the very same apparent discrepancy with insulin sensitizer drugs as well as TDZ are
Iñaki, en la misma línea de lo que dice Lucila y Luca, el HOMA-IR (supongo que a nivel basal) aunque te dé una medida aproximada de resistencia a la insulina, el GTT a mí forma de ver las cosas te da más información pues está midiendo la respuesta a esa sobrecarga de glucosa y puedes darte una idea de si hay o no resistencia a la insulina o si hay algún problema en la función del páncreas. Y de hecho si la glicemia fue menor en tu grupo tratado puedes darte una idea de que quizá haya mejorado la sensibilidad a la insulina, pues a igual cantidad de insulina secretada la glucosa (supongo que basal) es menor. Igual si estas trabajando con ratones, creo que el test de tolerancia a la insulina va mejor.
A publication from our institute has suggested that HOMA-IR is not a sensitive measure of insulin sensitivity, and often does not catch changes in insulin sensitivity.
http://www.ncbi.nlm.nih.gov/pubmed/24353184
For that reason, I would trust your glycemia curves more.
I agree with many of the above, and it is possible that resveratrol is increasing insulin secretion in response to the glucose challenge, or improving insulin sensitivity of other tissues (possibly through improvements in microvascular function). However, it is also possible that it is not directly altering insulin sensitivity in your study, but in fact improving the insulin-independent effects of glucose uptake.
http://diabetes.diabetesjournals.org/content/57/7/1814.full
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