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Abnormal central noradrenergic neuronal activity in patients with diabetes mellitus
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ABNORMAL CENTRAL NORADRENERGIC NEURONAL ACTIVITY IN PATIENTS WITH DIABETES MELLITUS. H.S. Grunstein and G.A. Smythe, Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, NSW, Australia. Recent data indicate that glucose excess suppresses central noradrenergic neuronal activity (NNA) in animals and man and that this effect mediates suppression of the pituitary-adrenalaxis. However, the effect of chronic hyperglycemia, as occurs in diabetes mellitus, on the relationship between central NNA and the pituitary-adrenalaxis is not known. We therefore measured urinary total 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), the major metabolite of central norepinephrine and hence a marker of central NNA, and urinary free cortisol excretion in 24 h urine collections from subjects with maturity onset diabetes receiving oral hypoglycemic agents (Group 1) or diet alone (Group Z), insulin-treateddiabetics (Group 3) and age-matched controls. Diabetic subjects, compared to controls, had higher urinary cortisol/creatinineexcretion (16.34 vs 10.020.8, mean + SE, p < 0.001) and urinary cortisol/MHPG ratio (515 vs 35t5, p < 0.05), although no statistical difference was found for urinary MHPG/creatinine excretion. The relationship between urinary cortisol/creatinine and MHPG/creatinine (expressed as the slope 2 SD of the regression line) revealed enhanced cortisol excretion relative to MHPG in diabetics (2517 vs 14%, controls, p <0.0005), On further analysis, this effect was seen in the slopes of the regression lines of Groups 1 (28%3, p < 0.005) and 2 (30215, p < 0.005), but not Group 3. The data reveal a disturbed relationship between urinary cortisol and MHPG in diabetic subjects. The data are consistent with abnormal central NNA in diabetes mellitus and this may be due to chronic hyperglycemia.
E8 DEVELOPMENTAL PATTERN OF ~PERINSULINEMIA AND INSULIN ~SISTANCE OF ADIPOSE TISSUE IN GENETICALLY OBESE MICE. L. Herberg, H.J. Partke and A. Schraven, Diabetes Forschungsinstitut,Univ. Misseldorf. Once established, hyperinsulinemia in mutants is thought to persist and either precede or increase an already established insulin resistance of adipose tissue. According to blood glucose in B1/6J-ob/ob and BL/KsJ-dbfdb -4 experimental periods were fixed: I=+day 6-16 (euglycemia), 11=18-22- (hypoglycemia), 1X=28-32 (euglycemia), IV=45-55 (hyperglycemia). Determinations: plasma insulin, fat cell size, body fat content, glucose metabolism of adipose tissue (oxidation and incorporation) in a, &, AvY (BL/6J) and db (BL/KsJ) mutants (mu) and controls (c). Results: blood glucose, plasma insulin and fat call size are influenced by line (mu or c), age and interaction line x age. Glucose metabolism is affected by line, age, insulin concentration (O-1000 ngt'mlfand interaction line x age. Glucose metabolism remains similar in mu and c at periods I and II with higher and lower pl. insulin resp. in mu. Glucose metabolism is depressed in mu at III and IV with pl. insulin similar and higher resp. in mu. Fat cell size and body fat content are higher in mu at all periods. The lack of any direct relationship in mu between plasma insulin and lipogenesis in periods I-III suggests that alterations in both D-cell function and lipogenesis in adipocytes already start before or shortly after birth.
ABNORMAL CENTRAL NORADRENERGIC NEURONAL ACTIVITY IN PATIENTS WITH DIABETES MELLITUS. H.S. Grunstein and G.A. Smythe, Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, NSW, Australia. Recent data indicate that glucose excess suppresses central noradrenergic neuronal activity (NNA) in animals and man and that this effect mediates suppression of the pituitary-adrenalaxis. However, the effect of chronic hyperglycemia, as occurs in diabetes mellitus, on the relationship between central NNA and the pituitary-adrenalaxis is not known. We therefore measured urinary total 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), the major metabolite of central norepinephrine and hence a marker of central NNA, and urinary free cortisol excretion in 24 h urine collections from subjects with maturity onset diabetes receiving oral hypoglycemic agents (Group 1) or diet alone (Group Z), insulin-treateddiabetics (Group 3) and age-matched controls. Diabetic subjects, compared to controls, had higher urinary cortisol/creatinineexcretion (16.34 vs 10.020.8, mean + SE, p < 0.001) and urinary cortisol/MHPG ratio (515 vs 35t5, p < 0.05), although no statistical difference was found for urinary MHPG/creatinine excretion. The relationship between urinary cortisol/creatinine and MHPG/creatinine (expressed as the slope 2 SD of the regression line) revealed enhanced cortisol excretion relative to MHPG in diabetics (2517 vs 14%, controls, p <0.0005), On further analysis, this effect was seen in the slopes of the regression lines of Groups 1 (28%3, p < 0.005) and 2 (30215, p < 0.005), but not Group 3. The data reveal a disturbed relationship between urinary cortisol and MHPG in diabetic subjects. The data are consistent with abnormal central NNA in diabetes mellitus and this may be due to chronic hyperglycemia.
E8 DEVELOPMENTAL PATTERN OF ~PERINSULINEMIA AND INSULIN ~SISTANCE OF ADIPOSE TISSUE IN GENETICALLY OBESE MICE. L. Herberg, H.J. Partke and A. Schraven, Diabetes Forschungsinstitut,Univ. Misseldorf. Once established, hyperinsulinemia in mutants is thought to persist and either precede or increase an already established insulin resistance of adipose tissue. According to blood glucose in B1/6J-ob/ob and BL/KsJ-dbfdb -4 experimental periods were fixed: I=+day 6-16 (euglycemia), 11=18-22- (hypoglycemia), 1X=28-32 (euglycemia), IV=45-55 (hyperglycemia). Determinations: plasma insulin, fat cell size, body fat content, glucose metabolism of adipose tissue (oxidation and incorporation) in a, &, AvY (BL/6J) and db (BL/KsJ) mutants (mu) and controls (c). Results: blood glucose, plasma insulin and fat call size are influenced by line (mu or c), age and interaction line x age. Glucose metabolism is affected by line, age, insulin concentration (O-1000 ngt'mlfand interaction line x age. Glucose metabolism remains similar in mu and c at periods I and II with higher and lower pl. insulin resp. in mu. Glucose metabolism is depressed in mu at III and IV with pl. insulin similar and higher resp. in mu. Fat cell size and body fat content are higher in mu at all periods. The lack of any direct relationship in mu between plasma insulin and lipogenesis in periods I-III suggests that alterations in both D-cell function and lipogenesis in adipocytes already start before or shortly after birth.