Dear Md. Nasir,

Maybe an experiment like this will give you some clues:

Find the saturation concentration for each: plant extract and glibenclamide, and then try to find out if you can increase the effect observed by adding both. This will give you at least a hint if the effects that you are observing are similar or not.

Overall, it's the reduction of blood glucose. On low level, you have many possibilities:

- increased glucose uptake and storage

- selective uptake by skeletal muscle or adipose tissue

- increased excretion

- increased metabolic rate

- etc etc.

There are many unanswered and unasked questions! Lots of possibilities for doing research: Which are the key compounds involved, where and how do they act, may these plants become a cheap and thus affordable treatment for diabetes? Are there new lead structures and new pathways for treating the disease?

No, you can not say that, at the moment there are several mechanisms of action for antidiabetics (antihyperglycemic) drugs and that depends also on the model of diabetes in animals you use or choose. There are insulin sensitizers, insulin secretors, incretins, etc.; commonly extract are not pure molecules, they can act on several receptors both.

Thanks both of you.

I have a question to clarify more:

Could we specify what type of diabetics has possibility to cure with this type of experiment, type 1 or type 2???

Dear Md. Nasir Ahmed,

This is why I told you that that depend of the diabetic animal model that you choose. Because there are many models of type 1 and type 2 diabetes. All experiments on animal models are not designed to permanently cure these animals, but to see if these treatments can improve some key parameters such as the concentration of insulin, glucagon, beta cell number, to see the improve of glucose uptake, etc. So to answer succinctly, none of type 1 diabetes or type 2 can be cured by these experiments.

Thank you Dr. Nyemb

Some investigations must be done to suggest the mechanism of action. These include intestinal glucose absorption, peripheral glucose uptake by muscle and adipose tissue and effect on GLUT4, hepatic glucose output (effect on gluconeogenic and glycogenic and glycogenolytic enzymes), insulin sensitivity and insulin signaling pathways.

Dr. Osama M. Ahmed

Dr. Osama

To do these investigations at first what should I do? I dont have phytochemical analysis of the medicinal plants, Should I do it firstly?

After proving that the agent has anti-hyperglycemic effects, in vivo, in vitro and in situ studies must be performed. Several techniques must be assessed including spectrophotometeric, molecular biology techniques, immunohistochemical, ELISA and RIA

Thanks a lot Dr. Osama

Dear Dr Nasir Ahmed,

In order to assess the overall insulinsensitivity for your animals, one the usefull and powerfull test is the euglycaemic-hyperinsulinemic clamp. That's an in vivo test.

You can take a look at this review :

http://www.ncbi.nlm.nih.gov/pubmed/17957034

It also does exist in vivo tests with radiotracer, analog of glucose, for instance : FDG, 6DIG, 3OMG....

http://www.ncbi.nlm.nih.gov/pubmed?term=6DIG

Best regards

I will check the link definitely Dr. Stephane Grauzam,...

Thanks for your contribution regarding my topic

Dear Nasir

You can try with

www.europeanreview.org/article/925

Mr. Sushil Middha...

Your article related to the alloxan induced diabetic rats but here my animal model is "Glucose induced Antihyperglycemic Mice"

Anyway Thanks for the link

Ya true Prof Ahmed, there are several ways to suggest the mechanism of action. Mostly glucose absorption, Tolerance tests Insulin/Glucose and uptake by muscles

Effect could also be exerted through antioxidants properties of the plant in question,since some of the phytochemicals possess such properties. Also some enzyme inhibitors of glycogenic,gluconeogenesis ,glycolytic and polyol pathways.

Dr Nafisa Could you shortly elaborate your thoughts please?

Could you provide me any protocol, Dr. Ahmed

You can follow the same article, whatever i have sent you

Dear Nasir,

Firstly i appreciate your instinctive question on plant extracts. The beauty of this question and the answer for the same lies in the ancient treatise of charaka samhita of Ayurveda - commentary by acharya chakrapani.

Regards,

Research Scholar,

SAYRM,

AYVM,

Bangalore

There are many mechanism involve for hypoglycemic effects ......... some are discovered while some are yet to discovered.

The Phyto extract sometime show sometimes a unique way for Hypoglycemic action due to cocktail of various natural compound present there and sometimes they show synergistic action.

Of course there are various models for different types of Diabetic model on the basis of various physiological parameter or biochemical markers which may altered or repaired during treatments.

I suggest to kindly search article with key words " Hypoglycemic action type 1/2 Diabetic"". Hope u got a series of articles .

or search it with for various models "" " Hypoglycemic action type 1/2 Diabetic model""".

Nasir, as u know in diabetic disorder, hyperglycemia is a major characteristic. This results to increased flux of glucose to the polyol pathway,increased production of reactive oxygen species/free radicals,non enzymic glycation etc. Major therapeutic appoach to treat DM is decrease post parandial hyperglycemia thru retarding digestion and absorption of glucose thru inhibition of carbohydrate hydrolyzin enzymes such as alpha glucosidase and alpha amylase or stimulate betacell of pancreas to release or resist hormones wch raise bld glucos or enhanc organ glucos OR free radical scavengin OR resist lipid peroxidation and correct metabolic disorder of lipid and protein OR prevent formation/accumulation of sorbitol in non insulin utilizing tissues such as lens. Synthetic drugs dependin on mode of action exerts one of d above actions to control diabetes and its complications. Medicinal plants owe there therapeutic anti diabetic effects tru their phytochemicals/secondary metabolites. It is speculated oxidativ stress causes most of the complications of most diseasea diabetes inclusive as such use of antioxidants is one good therapeutic approach. Invitro and invivo antioxidant study of plant in question gives idea whether plant has antioxidant property. You can look into review of medinal plants used in folkoloric medicine to treat DM

There is considerable diversity in the mechanisms of action of antdiabetic plants. Some act by increasing the release of insulin. Others by increasing insulin sensitivity. There are others that act by decreasing basal hepatic glucose production, thereby reducing fasting plasma glucose. Some block enzymatic degradation of complex carbohydrates in the small intestine, thereby lowering postprandial glucose. There are several other mechanisms as have been highlighted already by some contributors. This shows that antidiabetic plants do not operate by a single mechanism. The use of glibenclamide as reference drug in diabetic work may not be sufficient to decipher the actual mechanism of action of antidiabetic plants, except the plants operate like sulfonylureas. I suggest you go through the review article by Ivorra et al. In this article, the different mechanisms of actions of several antidiabetic plants were highlighted [ Ivorra MD, Paya M and Villar A (1989) A review of natural products and Plants as potential antidiabetic drugs. Journal of Ethnopharmacology 27:243-275.

One other mechanism by which extracts cause a reduction in blood glucose is by the inhibition of enzymes such as glucosidases and amylases thereby delaying the breakdown of polysaccharides.