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제42차 대한비만학회
춘계학술대회
Joint Symposium between KSMBS and KSSO II:
Diabetes Remission after Metabolic/Bariatric Surgery: Deciphering the Mechanisms Involved.
Possible Roles of GIP, the Incretin Twin of GLP-1
Division of Metabolism and Biosystemic Science, Department of Internal Medicine, Asahikawa
Medical University, Japan
Yukihiro Fujita, M.D., Ph.D.
Incretins such as glucose-dependent insulinotropic
blasts and adipocytes. GIPR-null mice actually mani-
polypeptide (GIP) and glucagon-like peptide-1 (GLP-1)
fests increased glucose excursion with reduction of
are gastrointestinal hormones that are released in re-
glucose-stimulated insulin secretion after an oral glu-
sponse to nutrient intake and promote insulin secretion.
cose load. In contrast, nutrient-enhanced GIP secretion
Incretins are thought to be responsible for up to 50% of
can be observed in rodents fed with high-fat diet and
postprandial insulin secretion in healthy subjects. Not
human obese subjects, which may promote fat deposi-
only GLP-1 but also GIP is the pharmacological target
tion in adipose tissue. Genetic, pharmacological or im-
of dipeptidyl peptidase-4 (DPP-4) inhibitors, which en-
munological ablation of GIPR signaling can success-
hance the incretin effect via blocking degradation of in-
fully protect from diet-induced obesity via GIP-medi-
cretins and ameliorate hyperglycemia in type2
ated fat accumulation. Therefore, it is proposed that
diabetes. GIP is released from K cells in gut mucosa,
GIP antagonism or suppressed GIP secretion via surgi-
which are more abundantly found in duodenum and je-
cal procedures might be beneficial as a potent treat-
junum, but less in ileum. Since some procedures for
ment for obesity.
bariatric surgery alter the nutrient flow by bypassing
However, some GIPR agonists did not induce obe-
the proximal gut, they can affect GIP secretion and its
sity but still improved hyperglycemia in type2 diabetic
actions.
rodent models, and high-fat diet did not promote obe-
GIP interacts with GIP receptor (GIPR) and increases intracellular cyclic AMP. GIPR is expressed in
sity in GIP over-expressing transgenic mice. Thus, further controversies over GIP action will be discussed.
various tissues including pancreatic beta cells, osteo-
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