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.