Kunos, George (National Institute on Alcohol Abuse and Alcoholism (NIAAA))
Jourdan, Tony (National Institute on Alcohol Abuse and Alcoholism (NIAAA))
Czech, Michael (University of Massachusetts Medical School)
Aouadi, Myriam (University of Massachusetts Medical School)
In vivo data available (animal)
The invention pertains to the use of glucan encapsulated non-immunostimulatory small interfering RNAs (siRNAs) to treat type-2 diabetes. Endocannabinoids (EC) are lipid signaling molecules that act on the same cannabinoid receptors that recognize and mediate the effects of endo- and phytocannabanoids. EC receptor CB1R activation is implicated in the development of obesity and its metabolic consequences, including insulin resistance and type 2 diabetes. Beta-cell loss has been demonstrated in a Zucker diabetic fatty (ZDF) rat model of type-2 diabetes through CB1R-mediated activation of a macrophage-mediated inflammatory response. Conversely, rats treated with a peripheral CB1R antagonist restores normoglycemia and preserves beta-cell function. Similar results are seen following selective in vivo knockdown of macrophage CB1R by daily treatment of ZDF rats with the instant D-glucan-encapsulated CB1R Small interfering RNA (siRNA). Knock-down of CB1R with using glucan encapsulated siRNA may represent a new commecializable method of treating type-2 diabetes or preventing the progression of insulin resistance to overt diabetes.
Treatment of obesity, insulin resistance, and diabetes.
A new means of inhibiting the endocannabinoid receptor CB1R.