Purinergic receptors on insulin-secreting cells

Summary— The insulin secreting B cell is fitted with the two types of purinergic receptors: P₂ (for ATP and/or ADP) and P₁ (for adenosine). The activation of P₂ purinoceptors by ATP or ADP evokes a biphasic stimulation of insulin secretion from isolated perfused rat pancreas; this stimulation is dose-dependent between 10^?6 and 10^?4 M. Non hydrolysable structural analogues are also effective, and the relative potency of various agonists (2-methylthio ATP ? ATP = ADP = α, β-methylene ATP ? AMP) gave evidence for a P_2y purinoceptor subtype. Proposed mechanisms include both an increased Ca²⁺ uptake and an increased intracellular Ca²⁺ mobilization via the hydrolysis of polyphosphoinositides. ATP (or ADP) potentiates physiological insulin-secreting agents (glucose and acetylcholine) and P₂ purinoceptors could play a physiological role in the stimulation of insulin secretion. The activation of P₁ purinoceptors (adenosine receptors) decreases insulin secretion. Using structural analogues of adenosine, the receptor was characterized as an A₁ subtype; it is coupled to a pertussis toxin sensitive G protein and it inhibits adenylate cyclase. It is of physiological relevance that the B cell has the two types of purinoceptors with opposite effects. Recently, a metabolically stable structural analogue of ADP, adenosine-5′-0-(2-thiodiphosphate) or ADPßS, has been described as a potent secretory agent, effective at nanomolar concentrations on isolated perfused rat pancreas. In vivo, this substance is able to increase insulin secretion and to improve glucose tolerance after IV administration in rats and oral administration in dogs. Furthermore in streptozotocin-induced diabetes, ADPßS retains its insulin secreting effects. These results suggest that P_2y purinoceptors could be a new target for antidiabetic drugs.     

INTRACEREBRAL HAEMORRHAGE IN A YOUNG ADULT: CONSIDER AMPHETAMINE ABUSE

SUMMARY We present the case of a young female who suffered a massive intracerebral bleed following the ingestion of a small quantity of amphetamine (speed). Physicians should be aware that amphetamine abuse can lead to cerebrovascular events in young adults.     

Association of an inter-arm systolic blood pressure difference with all-cause and cardiovascular mortality: A meta-analysis of cohort studies

This meta-analysis evaluated the potential association of a simultaneously measured inter-arm systolic blood pressure difference (IASBPD) and all-cause mortality and cardiovascular mortality. The Medline, Cochrane Library, Embase, and PubMed databases were searched through to April 14, 2023 for relevant literature. The outcomes were the associations of IASBPD with all-cause and cardiovascular mortality. Finally, 10 cohort studies that included 15 320 individuals were included. An IASBPD of ≥15 mm Hg was associated with increased all-cause mortality (pooled hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.02–1.61) but an IASBPD of ≥10 mm Hg was not (pooled HR 1.28, 95% CI 0.89–1.85). The pooled HR for cardiovascular mortality was 1.88 (95% CI 1.31–2.71) for an IASBPD of ≥10 mm Hg and 1.93 (95% CI 1.24–2.99) for an IASBPD of ≥15 mm Hg. Subgroup analysis showed that younger patients (HR 9.03, 95% CI 2.00–40.82, p = .004) with an IASBPD ≥15 mm Hg were at higher risk of cardiovascular mortality than older patients (HR 1.67, 95% CI 1.06–2.64, p = .03); the difference between groups was statistically significant (p = .04). In conclusions, our findings show that a simultaneously measured IASBPD ≥15 mm Hg predicts increased all-cause mortality and an IASBPD of ≥15 mm Hg or ≥10 mm Hg predicts increased cardiovascular mortality. An IASBPD ≥15 mm Hg appears to be more correlated with cardiovascular mortality in younger patients than in older patients.     

A rare case of cardiogenic shock caused by takotsubo syndrome associated with SARS-CoV-2 infection: The value of echocardiography in the diagnosis and monitoring of the efficacy of extracorporeal membrane oxygenation

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mainly invades the respiratory system, but may also cause various cardiovascular complications. We report a rare case of myocarditis associated with SARS-CoV-2 infection. A 61-year-old man was admitted to the hospital with a positive nucleic acid test for SARS-CoV-2. A sudden increase in troponin level (up to .144 ng/mL) was observed on the 8th day after admission. He developed symptoms of heart failure and progressed rapidly to cardiogenic shock. Echocardiography on the same day showed reduced left ventricular ejection fraction, reduced cardiac output, and segmental ventricular wall motion abnormalities. Takotsubo cardiomyopathy associated with SARS-CoV-2 infection was considered based on the typical echocardiography findings. We immediately started veno-arterial extracorporeal membrane oxygenation (VA-ECMO) treatment. The patient was successfully withdrawn from VA-ECMO after 8 days following recovery of ejection fraction to 65% and all indicators qualifying the withdrawal criteria. Echocardiography plays an important role in dynamic monitoring of cardiac changes in such cases and can help determine the timing of extracorporeal membrane oxygenation treatment and withdrawal.