Framework integrity is retained when water molecules replace the nitromethane molecules in the coordination polymer [Ag(hat)ClO ]⋅2 CH NO (see picture for structure), which are arranged in a helical fashion within the chiral micropores of the three-dimensional [Ag(hat) ] network with a (10,3)-a topology. Remarkably, this is also the case after subsequent displacement of the water by nitromethane molecules. hat=1,4,5,8,9,12-hexaazatriphenylene.

Our aim was to determine whether vagal transmission is required for the hormonal response to insulin-induced hypoglycemia in 18-h-fasted conscious dogs. Hollow coils were placed around the vagus nerves, with animals under general anesthesia, 2 wk before an experiment. On the day of the study they were perfused with −15°C ethanol for the purpose of blocking vagal transmission, either coincident with the onset of insulin-induced hypoglycemia or after 2 h of established hypoglycemia. In a separate study the coils were perfused with 37°C ethanol in a sham cooling experiment. The following parameters were measured: heart rate, arterial plasma glucose, insulin, pancreatic polypeptide, glucagon, cortisol, epinephrine, norepinephrine, glycerol, free fatty acids, and endogenous glucose production. In response to insulin-induced hypoglycemia (42 mg/dl), plasma glucagon peaked at a level that was double the basal level, and plasma cortisol levels quadrupled. Plasma epinephrine and norepinephrine levels both rose considerably to 2,135 ± 314 and 537 ± 122 pg/ml, respectively, as did plasma glycerol (330 ± 60%) and endogenous glucose production (150 ± 20%). Plasma free fatty acids peaked at 150 ± 20% and then returned to basal levels by the end of the study. The hypoglycemia-induced changes were not different when vagal cooling was initiated after the prior establishment of hypoglycemia. Similarly, when vagal cooling occurred concurrently with the initiation of insulin-induced hypoglycemia (46 mg/dl), there were no significant differences in any of the parameters measured compared with the control. Thus vagal blockade did not prevent the effect on either the hormonal or metabolic responses to low blood sugar. Functioning vagal afferent nerves are not required for a normal response to insulin-induced hypoglycemia.

We investigated the effect of inhibiting glycogenolysis on gluconeogenesis in 18-h-fasted conscious dogs with the use of intragastric administration of BAY R 3401, a glycogen phosphorylase inhibitor. Isotopic ([3-3H]glucose and [U-14C]alanine) and arteriovenous difference methods were used to assess glucose metabolism. Each study consisted of a 100-min equilibration, a 40-min control, and two 90-min test periods. Endogenous insulin and glucagon secretions were inhibited with somatostatin (0.8 μg ⋅ kg−1 ⋅ min−1), and the two hormones were replaced intraportally (insulin: 0.25 mU ⋅ kg−1 ⋅ min−1; glucagon: 0.6 ng ⋅ kg−1 ⋅ min−1). Drug (10 mg/kg) or placebo was given after the control period. Insulin and glucagon were kept at basal levels in the first test period, after which glucagon infusion was increased to 2.4 ng ⋅ kg−1 ⋅ min−1; BAY R 3401 decreased tracer-determined endogenous glucose production [rate of glucose production (Ra): 14 ± 1 to 7 ± 1 μmol ⋅ kg−1 ⋅ min−1] and net hepatic glucose output (11 ± 1 to 3 ± 2 μmol ⋅ kg−1 ⋅ min−1) during test 1. It increased the net hepatic uptake of gluconeogenic substrates from 9.0 ± 2.0 to 11.6 ± 0.6 μmol ⋅ kg−1 ⋅ min−1. Basal glycogenolysis was decreased by drug (9.1 ± 0.7 to 1.5 ± 0.2 μmol glucosyl U ⋅ kg−1 ⋅ min−1). Placebo had no effect on Ra or the uptake of gluconeogenic precursors by the liver. The rise in glucagon increased Ra by 22 ± 3 and by 8 ± 2 μmol ⋅ kg−1 ⋅ min−1(at 10 min) in placebo and drug, respectively. The rise in glucagon caused little change in the net hepatic uptake (μmol ⋅ kg−1 ⋅ min−1) of gluconeogenic substrates in placebo (8.2 ± 0.6 to 9.0 ± 1.0) but increased it markedly (11.6 ± 0.6 to 15.4 ± 1.0) in drug. Glucagon increased glycogenolysis by 22.1 ± 2.5 and by 7.8 ± 1.6 μmol ⋅ kg−1 ⋅ min−1in placebo and drug, respectively. The amount of glycogen (μmol glucosyl U/kg) synthesized from gluconeogenic carbon was four times higher in drug (48.6 ± 9.7) than in placebo (11.3 ± 1.7). We conclude that BAY R 3401 caused a marked reduction in basal and glucagon-stimulated glycogenolysis. As a result of these changes, there was an increase in the net hepatic uptake of gluconeogenic precursors and in glycogen synthesis.

Our aim was to determine whether complete hepatic denervation would affect the hormonal response to insulin-induced hypoglycemia in dogs. Two weeks before study, dogs underwent either hepatic denervation (DN) or sham denervation (CONT). In addition, all dogs had hollow steel coils placed around their vagus nerves. The CONT dogs were used for a single study in which their coils were perfused with 37 degrees C ethanol. The DN dogs were used for two studies in a random manner, one in which their coils were perfused with -20 degrees C ethanol (DN + COOL) and one in which they were perfused with 37 degrees C ethanol (DN). Insulin was infused to create hypoglycemia (51 +/- 3 mg/dl). In response to hypoglycemia in CONT, glucagon, cortisol, epinephrine, norepinephrine, pancreatic polypeptide, glycerol, and hepatic glucose production increased significantly. DN alone had no inhibitory effect on any hormonal or metabolic counterregulatory response to hypoglycemia. Likewise, DN in combination with vagal cooling also had no inhibitory effect on any counterregulatory response except to reduce the arterial plasma pancreatic polypeptide response. These data suggest that afferent signaling from the liver is not required for the normal counterregulatory response to insulin-induced hypoglycemia.