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Glucagon-Like Peptide 1 (GLP-1) has insulin-like effects on myocardial glucose uptake which may contribute to its beneficial effects in the setting of myocardial ischemia. Whether these effects are different in the setting of obesity or type 2 diabetes (T2DM) requires investigation. We examined the cardiometabolic actions of GLP-1 (7–36) in lean and obese/T2DM humans, and in lean and obese Ossabaw swine. GLP-1 significantly augmented myocardial glucose uptake under resting conditions in lean humans, but this effect was impaired in T2DM. This observation was confirmed and extended in swine, where GLP-1 effects to augment myocardial glucose uptake during exercise were seen in lean but not in obese swine. GLP-1 did not increase myocardial oxygen consumption or blood flow in humans or in swine. Impaired myocardial responsiveness to GLP-1 in obesity was not associated with any apparent alterations in myocardial or coronary GLP1-R expression. No evidence for GLP-1 mediated activation of cAMP/PKA or AMPK signaling in lean or obese hearts was observed. GLP-1 treatment augmented p38-MAPK activity in lean, but not obese cardiac tissue. Taken together, these data provide novel evidence indicating that the cardiometabolic effects of GLP-1 are attenuated in obesity and T2DM, via mechanisms that may involve impaired p38-MAPK signaling.

Neurofibromatosis type 1 (NF1) is associated with vascular lesions, such as renal artery stenosis, and secondary hypertension. The real prevalence is largely unknown, particularly in children. We observed 27 patients with NF1, mean age 12.8 years (range 4.2-24 years), for 2-10 years to assess the association of NF1 with vascular abnormalities and secondary hypertension. Patients were studied with angiography, 24-h blood pressure monitoring, a captopril test, and Doppler ultrasonography of aorta and renal arteries. The prevalence of hypertension was 18.5%; 61.5% of patients studied with angiography had vascular lesions, half of whom were apparently normotensive. However, they had abnormal 24-h blood pressure monitoring, which was a first sign of poor blood pressure control. Those patients with severe hypertension (11.1%) were successfully treated with percutaneous transluminal angioplasty (PTA); stenosis recurred in 2 of 3 patients after a 2-year follow-up period, and was responsive to drugs. We conclude that hypertension is a frequent complication of NF1 in pediatric patients, it is usually secondary to typical vascular lesions, and requires careful follow-up. Ambulatory blood pressure monitoring (24-h) is a sensitive method for detecting initial alterations of the blood pressure pattern. PTA may be an effective treatment in this condition.

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