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The authors investigated the effects of clonidine (alpha-2 stimulating agent) on blood glucose, insulin and glucagon levels in order to assess the alpha-adrenergic regulation of endocrine pancreatic secretion. Ten hypertensive female subjects affected with type 2 diabetes were studied; each subject was given a protein meal (boiled beef 200 g); blood samples were taken at -30, 0, 30, 60, 90 and 120 min; after this test each subject was treated for 4 days with clonidine (0.150 mg, 3 times/day per os); at the 5th day the protein meal was repeated under the same conditions except for the added administration of clonidine. Plasma glucose, insulin and glucagon were estimated. The administration of a protein meal caused a significant increase of blood glucose (peak at 60 min), insulin (peak at 90 min) and glucagon (peak at 90 min) levels; the association of clonidine caused an increase of blood glucose (single values and total areas) without changes of insulin and glucagon levels, when compared to those obtained before clonidine treatment. In conclusion, the association of clonidine to a protein meal caused impaired glucose tolerance presumably due to a direct glycogenolytic effect, occurring in the liver on account of an alpha-2 receptor stimulation, insulin and glucagon not being involved in this phenomenon.