Received September 28, 2006
Revised November 9, 2006
Accepted after revision February 1, 2007
Neuroendocrinology/Endocrinology [270]
|
Sharpey-Schafer Prize Lecture. Physiological regulation
of the pancreatic beta-cell: Functional insights for
understanding and therapy of diabetes
Neville H McClenaghan 1*
1 University of Ulster
* To whom correspondence should be addressed. E-mail: nh.mcclenaghan{at}ulster.ac.uk.
 |
Abstract |
|---|
Knowledge into the sites and actions of the numerous
physiological and pharmacological factors affecting
insulin secretion and pancreatic beta-cell function has
been derived from the use of bioengineered insulin-
producing cell lines. Application of an innovative
electrofusion approach has generated novel glucose-
responsive insulin-secreting cells for pharmaceutical
and experimental research, including popular BRIN-BD11
cells. This review gives an overview of the
establishment and core characteristics of clonal
electrofusion-derived BRIN-BD11 beta-cells. As
discussed, BRIN-BD11 cells have facilitated studies
aimed at dissecting important pathways by which
nutrients and other bioactive molecules regulate the
complex mechanisms regulating insulin secretion, and
highlight the future potential of novel and diverse
bioengineering approaches to provide a cell-based
insulin-replacement therapy for diabetes. Clonal BRIN-
BD11 beta-cells have been instrumental in (a)
characterizing KATP channel-dependent and -independent
actions of nutrients and established and emerging
insulinotropic antidiabetic drugs, and the understanding
of drug-induced beta-cell desensitization; (b) tracing
novel metabolic and beta-cell secretory pathways,
including use of state-of-the-art NMR approaches to
provide new insights into the relationships between
glucose and amino acid handling and insulin secretion;
and (c) determining the chronic detrimental pancreatic
beta-cell actions of nutrients and the diabetic
environment, including the recent discovery that
metabolic syndrome risk factor, homocysteine, may play a
role in the progressive demise of insulin secretion and
pancreatic beta-cell function in diabetes. Collectively,
the studies discussed in this review highlight the
importance of innovative experimental beta-cell
physiology in the discovery and characterization of new
and improved drugs and therapeutic strategies to help
tackle the emerging diabetes epidemic.
Key Words:
Cell signalling, Diabetes, Insulin
