OBJECTIVEWe tested the hypothesis that adrenergic activation, cholinergic activation, or both, mediate the effect of recent antecedent hypoglycemia to reduce the sympathoadrenal response to subsequent hypoglycemia, the key feature of hypoglycemia-associated autonomic failure in diabetes, in humans.RESEARCH DESIGN AND METHODSSeventeen healthy adults were studied on 2 consecutive days on three occasions. Day 1 involved hyperinsulinemic euglycemic (90 mg/dL × 1 h), then hypoglycemic (54 mg/dL × 2 h) clamps, in the morning and afternoon on all three occasions with 1) saline infusion, 2) adrenergic blockade with the nonselective α-adrenergic and β-adrenergic antagonists phentolamine and propranolol, or 3) adrenergic blockade plus cholinergic blockade with the muscarinic cholinergic antagonist atropine in random sequence. Day 2 involved similar morning euglycemic and hypoglycemic clamps, with saline infusion, on all three occasions.RESULTSCompared with the responses to hypoglycemia during saline infusion on day 1, the plasma epinephrine and norepinephrine responses to hypoglycemia were reduced on day 2 (351 ± 13 vs. 214 ± 22 pg/mL for epinephrine and 252 ± 4 vs. 226 ± 7 pg/mL for norepinephrine during the last hour; both P < 0.0001). However, the plasma epinephrine and norepinephrine responses to hypoglycemia were not reduced on day 2 when adrenergic or adrenergic plus cholinergic blockade was produced during hypoglycemia on day 1.CONCLUSIONSAdrenergic blockade prevents the effect of hypoglycemia to reduce the plasma catecholamine responses to subsequent hypoglycemia. Thus, adrenergic activation mediates the effect of recent antecedent hypoglycemia to reduce the sympathoadrenal response to subsequent hypoglycemia, the key feature of hypoglycemia-associated autonomic failure in diabetes, in humans.
OBJECTIVEWe tested the hypotheses that in nondiabetic individuals, partial inhibition of insulin secretion with the ATP-sensitive K+ channel agonist (opener) diazoxide, compared with placebo, results in higher plasma glucose and higher plasma glucagon concentrations after a mixed meal and after administration of the sulfonylurea glimepiride.RESEARCH DESIGN AND METHODSPlasma glucose, insulin, C-peptide, and glucagon concentrations were measured every 30 min from −60 through 180 min with random-sequence, double-blind administration of diazoxide (6.0 mg/kg) or placebo at −30 and 1 min, ingestion of a formula mixed meal (Ensure Plus) at 0 min after diazoxide and after placebo and, on a separate occasion, ingestion of glimepiride (4.0 mg) at 0 min (with glucose infused to prevent hypoglycemia) after diazoxide and after placebo in 11 healthy young adults.RESULTSWith diazoxide administration, insulin (P = 0.0016) and C-peptide (P = 0.0287) concentrations were decreased and glucose concentrations were increased (e.g., 180-min values of 106 ± 4 mg/dL [5.9 ± 0.2 mmol/L] compared with 87 ± 2 mg/dL [4.8 ± 0.1 mmol/L] with placebo; P < 0.0001), but glucagon concentrations were no different after the mixed meal. Similarly, with diazoxide, C-peptide concentrations were decreased (P = 0.0015) and glucose concentrations were increased (P < 0.0001), but glucagon concentrations declined similarly after glimepiride administration.CONCLUSIONSPartial inhibition of insulin secretion results in impairment of glucose tolerance after a mixed meal and after glimepiride administration in the absence of a difference in glucagon secretion. They underscore the primary glucoregulatory role of insulin and support the evidence that β-cell secretion is not the only regulator of α-cell glucagon secretion.
Naga Parpam is a Zinc Oxide based nano medicine, used in Siddha system. Physiochemical analysis is done for standardization of this medicine and to have knowledge of the working principle of this medicine. It has anticancer activity and it is seen in autoimmune diseases, there is a definite imbalance in the metals and in cancer, Zinc is depleted in cell level whereas it is accumulated in the blood plasma. Hence, for substitution of Zinc, it has to penetrate the cells and also it should be non-toxic, for which, Naga Parpam is considered. FTIR, SEM, EDAX, XRD and PL studies were done. The morphology shows that in Naga Parpam there are different sized particles, which falls in the nano size. This shows that this drug can penetrate at different penetration depths. Presence of Zinc, Oxygen, Silicon, Magnesium and Potassium has been established by EDAX studies. FTIR confirms the presence of ZnO, SiO2 and Mg. XRD confirms the presence of ZnO in hexagonal wurtzite structure. Secondary phase is seen, which is mainly due to Mg present in the sample. The broad peak at 525 nm, which is the characteristic peak for ZnO, from the PL studies also shows the disruption of structure due to the presence of Mg, which is also confirmed by the secondary phase in XRD. It is concluded that Naga Parpam is a potential candidate for substitution of Zn, in Zn depleted auto immune diseases and also in cancer.
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