Molecular Genetics of Diabetes Mellitus 
found throughout the gastrointestinal tract, in- 
cluding the pancreas, and nervous systems. It has 
many diverse functions, including inhibiting the 
secretion of insulin and glucagon from the cells 
of the pancreatic islets and of growth hormone 
from the pituitary. In the central nervous system, 
somatostatin acts as a neurotransmitter to regu- 
late neuronal activity and to facilitate the release 
of other neurotransmitters. It may also play a role 
in centrally mediated behaviors such as move- 
ment and cognition. We have recently cloned 
the genes encoding three somatostatin receptors. 
All are members of the seven-transmembrane- 
spanning, GTP-binding protein family of recep- 
tors. One of these, SSTR2, is expressed in the pan- 
creatic /S-cell and is likely to be responsible for 
mediating the inhibition of insulin release by so- 
matostatin. The three somatostatin receptor iso- 
forms that we have characterized have unique 
pharmacological properties and couple to differ- 
ent intracellular effector systems, thus providing 
at least a partial explanation for the diverse physi- 
ological effects of somatostatin. We are continu- 
ing our studies of this family of receptors to gain a 
better understanding of how somatostatin bind- 
ing results in inhibition of insulin secretion. 
In addition to genes expressed in the pancre- 
atic /3-cell, we have also characterized genes for 
membrane proteins involved in the transport of 
glucose across the plasma membrane. Our stud- 
ies have revealed unexpected functional com- 
plexity that could have important implications 
for the treatment of diabetes. These studies indi- 
cate that facilitative glucose transport is not the 
property of a single protein but rather involves a 
family of at least five structurally related pro- 
teins. These proteins have distinct patterns of tis- 
sue distribution and different kinetic properties 
and are independently regulated. These features 
allow the precise disposal of dietary glucose 
under varying physiological conditions. Recent 
studies have shown that one of the five proteins 
we have identified is the major glucose trans- 
porter of neuronal cells and that the major func- 
tion of another is to transport fructose across the 
plasma membrane. This fructose transporter is 
expressed on the luminal surface of the absorp- 
tive epithelial cells of the small intestine and kid- 
ney tubules and is also present in early and late 
spermatids in the testes. Sperm require a fructose 
transporter, because they utilize fructose in semi- 
nal fluid as an energy source. 
Our studies are leading to a better understand- 
ing of the causes of diabetes mellitus. In addition, 
they are providing new insight into the function 
of somatostatin in the regulation of neuronal 
function. The identification of the fructose trans- 
porter in sperm may also have implications in re- 
productive physiology. Our results also illustrate 
how studies in one area can impact those in an- 
other, because of the exquisite manner in which 
the organism is able to utilize similar proteins for 
different physiological functions. 
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