N-Hydroxyethyl-1-Deoxynojirimycin (Miglitol) Restores the Counterregulatory Response to Hypoglycemia Following Antecedent Hypoglycemia.

Antecedent hypoglycemia suppresses the counterregulatory responses to subsequent hypoglycemic episodes, which can be prevented by normalizing portal-mesenteric vein (PMV) glycemia alone during the antecedent bout. Since the sodium-glucose transporter 3 receptor has been implicated in PMV glucosensing, we hypothesized that PMV infusion of the sodium-glucose cotransporter 3 receptor agonist N-hydroxyethyl-1-deoxynojirimycin (miglitol) would rescue the sympathoadrenal response to subsequent hypoglycemia. Rats underwent hyperinsulinemic-hypoglycemic clamps on 2 consecutive days without miglitol infusion (antecedent hypoglycemia without miglitol [HYPO]) or with miglitol infused upstream in the PMV, perfusing the glucosensors, or adjacent to the liver, bypassing PMV glucosensors, on day 1 or day 2. Control animals underwent day 1 euglycemic clamps, followed by hypoglycemic clamps on day 2. Peak epinephrine (EPI) responses for HYPO on day 2 were significantly blunted when compared with controls. Miglitol infusion on day 1 proved ineffective in restoring the EPI response following antecedent hypoglycemia, but day 2 miglitol infusion restored EPI responses to control levels. As norepinephrine and glucagon demonstrated similar responses, day 2 administration of miglitol effectively restored the counterregulatory response following antecedent hypoglycemia. In subsequent experiments, we demonstrate similar results with reduced miglitol infusion doses, approaching those currently prescribed for type 2 diabetes (correcting for rodent size), as well as the efficacy of oral miglitol administration in restoring the counterregulatory responses following antecedent hypoglycemia.

The chemistry and pharmacology of synthetic cannabinoid SDB-006 and its regioisomeric fluorinated and methoxylated analogs.

Synthetic cannabinoids are the largest and most structurally diverse class of new psychoactive substances, with manufacturers often using isomerism to evade detection and circumvent legal restriction. The regioisomeric methoxy- and fluorine-substituted analogs of SDB-006 (N-benzyl-1-pentyl-1H-indole-3-carboxamide) were synthesized and could not be differentiated by gas chromatography-mass spectrometry (GC-MS), but were distinguishable by liquid chromatography-quadrupole time-of-flight-MS (LC-QTOF-MS). In a fluorescence-based plate reader membrane potential assay, SDB-006 acted as a potent agonist at human cannabinoid receptors (CB1 EC50 = 19 nM). All methoxy- and fluorine-substituted analogs showed reduced potency compared to SDB-006, although the 2-fluorinated analog (EC50 = 166 nM) was comparable to known synthetic cannabinoid RCS-4 (EC50 = 146 nM). Using biotelemetry in rats, SDB-006 and RCS-4 evoked comparable reduction in body temperature (~0.7°C at a dose of 10 mg/kg), suggesting lower potency than the recent synthetic cannabinoid AB-CHMINACA (>2°C, 3 mg/kg).

Magnetically Induced Optical Transparency on a Forbidden Transition in Strontium for Cavity-Enhanced Spectroscopy.

In this Letter we realize a narrow spectroscopic feature using a technique that we refer to as magnetically induced optical transparency. A cold ensemble of ^{88}Sr atoms interacts with a single mode of a high-finesse optical cavity via the 7.5 kHz linewidth, spin forbidden ^{1}S_{0} to ^{3}P_{1} transition. By applying a magnetic field that shifts two excited state Zeeman levels, we open a transmission window through the cavity where the collective vacuum Rabi splitting due to a single level would create destructive interference for probe transmission. The spectroscopic feature approaches the atomic transition linewidth, which is much narrower than the cavity linewidth, and is highly immune to the reference cavity length fluctuations that limit current state-of-the-art laser frequency stability.

Superradiance on the millihertz linewidth strontium clock transition.

Laser frequency noise contributes a significant limitation to today's best atomic clocks. A proposed solution to this problem is to create a superradiant laser using an optical clock transition as its gain medium. This laser would act as an active atomic clock and would be highly immune to the fluctuations in reference cavity length that limit today's best lasers. We demonstrate and characterize superradiant emission from the millihertz linewidth clock transition in an ensemble of laser-cooled 87Sr atoms trapped within a high-finesse optical cavity. We measure a collective enhancement of the emission rate into the cavity mode by a factor of more than 10,000 compared to independently radiating atoms. We also demonstrate a method for seeding superradiant emission and observe interference between two independent transitions lasing simultaneously. We use this interference to characterize the relative spectral properties of the two lasing subensembles.