In 1997, there were 6567 publications about diabetes. In 2002, there were over 8600 publications (results of a PubMed search) having 'diabetes' in the medical subject heading (Rezaei-Ghaleh et al., 2004). Extensive current research is directed at understanding both types of diabetes on molecular bases. Numerous publications that do not have 'diabetes' in the title are not included in the numbers above, yet many have just as much relevance to elucidation of the molecular mechanisms of diabetes as those that do.

In particular, there is much current research of glucose-stimulated insulin secretion (GSIS), which is relative to type II diabetes. Below are just a few of many examples.

1) Ronnebaum et al. (2006) proposed further research of ICDc and its connection to NADPH levels and GSIS regulation, noting that the Experimental Evidence could also support a link between α-ketoglutarate and GSIS. Further studies to show whether NADPH is an important coupling factor for GSIS regulation were also proposed for some of the following reasons:

• NADPH is a cofactor for biosynthetic reactions, such as fatty acid synthesis and elongation that occur in β-cells.
• NADPH is a substrate for an enzyme that makes mevalonate, which is used for protein isoprenylation (addition of hydrophobic, or water-hating, molecules). Research shows a possible link between protein isoprenylation and GSIS.
• Both NADPH and ICDc may help to keep a redox status in β-cells, which would allow for insulin secretion.
• NADPH levels were shown to correlate with the rate of inactivation of voltage-dependent potassium channels, possibly prolonging the repolarization of cell membranes and allowing for efficient insulin secretion.

2) Shortly after the Ronnebaum et al. (2006) paper was published, Joseph et al. (2006) proposed that the mitochondrial citrate/isocitrate carrier helps regulate GSIS. Some of the Joseph et al. (2006) findings included: (a) both inhibition and adenovirus-mediated suppression of the carrier's activity in INS-1-derived 832/13 cells caused GSIS impairment in both phases and (b) overexpression of the CIC carrier increased GSIS.

3) Recently, Pongratz et al. (2007) published a proposal that the two differently compartmentalized isoforms of malic enzyme (cytosolic and mitochondrial, or ME1 and ME2, respectively) regulated insulin secretion differently. The report provided evidence that suppressing ME1 activity connected with decreased insulin secretion after cells were stimulated by both glucose and amino acids, whereas suppressing ME2 activity only decreased insulin secretion stimulated by increased concentrations of various amino acids.

4) Earlier, Suh et al. (2004) showed that overexpression of short heterodimer partner (SHP), a nuclear receptor in β-cells with unknown function, reversed the effects of impaired GSIS in pancreatic β-cells due to overexpression of mitochondrial uncoupling protein (UCP2). In islet cells not overexpressing UCP2, GSIS was increased. Overexpression of SHP in islets played a specific role in ATP-regulated potassium channels and in increasing the ATP/ADP ratio.

These findings and many others are slowly but surely shedding light on the whole mechanism of insulin secretion regulation and will hopefully one day lead to improved treatment for type II diabetes.