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.     

The Acne Disability Index: Usefulness confirmed

One hundred and four patients with acne completed a questionnaire derived from the Cardiff Acne Disability Index Questionnaire. In addition, 59% of patients returned an identical follow-up questionnaire 6 months later. Significant disability from acne was identified in many patients, with the median initial Acne Disability Index (ADI) being 6 (maximum possible 15), improving to 3 after treatment. Scores correlated poorly with the clinical severity of acne. The questionnaire proved useful for identifying patients with poor self-image who might benefit from more potent treatment for their acne, and to evaluate the effect of treatment.     

A novel mutation in a CARD14-associated papulosquamous eruption

CARD14-associated papulosquamous eruption (CAPE), a spectrum that includes clinical features of psoriasis and pityriasis rubra pilaris (PRP), is associated with activating mutations in the CARD14 gene. Herein we describe the clinical features of a family with CAPE and a novel mutation of CARD14, and highlight ectropion as part of the phenotypic spectrum of CAPE.