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VOL. 71 (2), 283-319, 2005 PURINERGIC SIGNALLING: THERAPEUTIC POTENTIAL

ATP-sensitive potassium channels in islet b-cells. Biotin enhances
ATP synthesis in pancreatic islets, resulting in reinforcement of
glucose-induced insulin secretion.

P2Y purinoceptors appear to be impaired in fibroblasts from Type
2 diabetic patients, which results in reduced glucose (GLUT 1)
uptake, suggesting that P2Y receptors may be candidate targets for
the design of innovative antidiabetic drugs. Hormone-specific defects
in insulin regulation of ATPase is seen in non-insulin-dependent
diabetic rats that may contribute to their insulin resistance.

A feature of diabetic retinopathy is the apoptotic death of
microvascular pericytes and endothelial cells; there appears to be an
enhancement of P2X7-induced pore formation and apoptosis in early
diabetes on the retinal microvasculature. In streptozotocin-diabetic
animals, P2X7 receptor expression, located in glucagon-containing a
cells in pancreatric islets, increases and migrates centrally to take
the place of the insulin-containing b-cells, although the functional
significance of this is not known. The potential role of purinergic
compounds as novel treatments for diabetes has yet to be explored.
Stimulation of insulin secretion and improvement of glucose
tolerance in rats and dogs by the P2Y receptor agonist adenosine-5’-
(2-thiodiphosphate) has been claimed.

ENDOCRINE AND FAT CELLS

Purinoceptors are widely expressed in endocrine glands (1). For
example, ATP and UTP increase cystolic free calcium in human
thyrocytes, ATP modulates aldosterone production by adrenal cortex,
ATP regulates prolactin release from anterior pituitary and
vasopressin and oxytocin secretion from posterior pituitary. ATP
stimulates insulin release from endocrine pancreas, ATP and UTP
inhibit oestrodial and progesterone secretion from the ovary and
mediate increases in intracellular calcium in Sertoli cells from testis.
Recent observations reveal a wide diversity of actions of purines in
the pituitary, including trophic effects and cytokine production as
well as actions in hormone release, with implications for pathological
as well as physiological states.

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