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Pancreastatin, a novel peptide, is known to inhibit insulin secretion and to have a glycogenolytic effect, and is present in many endocrine and chromaffin cells. Both the plasma insulin levels and the adrenergic activity accompanying insulin resistance have been shown to be increased in hypertensive subjects. Our working hypothesis was that pancreastatin might play a role in these pathological phenomena.We studied the plasma pancreastatin level in non-obese essential hypertensive patients in response to an intravenous glucose load. We further measured the responses to the glucose challenge of insulin, glucagon, catecholamines and free fatty acids, as well as other factors related to insulin resistance (i.e. lipoproteins and apolipoproteins). We separated the hypertensive patients into three groups according to their response to an oral glucose-tolerance test: normoinsulinaemic, hyperinsulinaemic and glucose-intolerant. Matched normotensive control subjects were also studied.Pancreastatin levels did not change in the control group after the glucose challenge. However, all hypertensive patients showed an increase in plasma pancreastatin levels after glucose loading. The normoinsulinaemic hypertensive patients also had elevated basal pancreastatin levels. The increase in pancreastatin levels was in the ranking: normoinsulinaemic hyperinsulinaemic glucose-intolerant. The pancreastatin: insulin ratio showed that the secretion of pancreastatin and insulin may be regulated differently. Basal free fatty acid and glucagon levels were found to be elevated both in the hyperinsulinaemic and in the glucose-intolerant group. Fasting triglycerides levels were increased in all of the hypertensive patients. Other risk factors for coronary artery disease were also found to be altered: elevated very low-density lipoprotein-cholesterol and decreased high-density lipoprotein-cholesterol, with ranking: normoinsulinaemic hyperinsulinaemic glucose-intolerant.These results show an increase in pancreastatin levels in hypertensive patients, suggesting that pancreastatin might play a role in the pathophysiology of essential hypertension.