• Korean Journal of Clinical Pharmacy
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• v.21 no.2
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• pp.57-65
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• 2011

Incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide delay gastric emptying, increasing satiety, and enhance insulin secretion. Two new classes of treatments related to incretin hormones for the management of type 2 diabetes mellitus have emerged: GLP-1 receptor agonists (e.g., exenatide, liraglutide) and the dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g., sitagliptin, saxagliptin, vildagliptin, alogliptin), which prevent the degradation of GLP-1. A MEDLINE search was conducted in order to evaluate the efficacy and safety of incretin-based therapies and publications were reviewed. Data from clinical trials indicated incretin-based treatment showed clinically significant reductions in hemoglobin A1c with low risk of hypoglycemia. Weight reductions were observed with GLP-1 receptor agonists where as DPP-4 inhibitors are weight neutral.

• Journal of Chest Surgery
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• v.21 no.3
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• pp.558-562
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• 1988

Localized mesothelioma is a primary pleural tumor that induces hypoglycemia rarely. We experienced a case of the localized mesothelioma that induced hypoglycemia. The patient was 70 year-old man who was admitted to Severance Hospital because of general weakness and mental confusion in morning before breakfast. He was found to have low level of fasting blood sugar and C-peptide, but had normal serum insulin level. After excision of the tumor, the patient was free from symptoms of hypoglycemia, and fasting blood sugar level was returned to normal range. The most likely speculation of causing hypoglycemia by the mesothelioma was thought to be that the tumor did not secrete insulin itself but the undetectable insulin-like substance and/or antigluconeogenic substances. During the follow up, 5 months after surgical removal of tumor, the patient was in a good condition without symptoms of hypoglycemia.

• Mass Spectrometry Letters
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• v.9 no.1
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• pp.17-23
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• 2018

Studies on the interactions of amyloidogenic proteins with trace metals, such as copper, have indicated that the metal ions perform a critical function in the early oligomerization process. Herein, we investigate the effects of Cu(II) ions on the active sequence regions of amyloidogenic proteins using electrospray ionization mass spectrometry (ESI-MS) and collision induced dissociation tandem MS (CID-MS/MS). We chose three amyloidogenic peptides NNQQNY, LYQLEN, and VQIVYK from yeast prion like protein Sup35, insulin chain A, and tau protein, respectively. [Cu-peptide] complexes for all three peptides were observed in the mass spectra. The mass spectra also show that increasing Cu(II) concentrations decrease the population of existing peptide oligomers. The tandem mass spectrum of NNQQNY shows preferential binding for the N-terminal region. All three peptides are likely to appear to be in a Cu-monomer-monomer (Cu-M-M) structure instead of a monomer-Cu-monomer (M-Cu-M) structure.

• BMB Reports
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• v.46 no.12
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• pp.606-610
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• 2013

Glucagon like peptide-1 (GLP-1) regulates glucose mediated-insulin secretion, nutrient accumulation, and ${\beta}$-cell growth. Despite the potential therapeutic usage for type 2 diabetes (T2D), GLP-1 has a short half-life in vivo ($t_{1/2}$ <2 min). In an attempt to prolong half-life, GLP-1 fusion proteins were genetically engineered: GLP-1 human serum albumin fusion (GLP-1/HSA), AGLP-1/HSA which has an additional alanine at the N-terminus of GLP-1, and AGLP-1-L/HSA, in which a peptide linker is inserted between AGLP-1 and HSA. Recombinant fusion proteins secreted from the Chinese Hamster Ovary-K1 (CHO-K1) cell line were purified with high purity (>96%). AGLP-1 fusion protein was resistant against the dipeptidyl peptidase-IV (DPP-IV). The fusion proteins activated cAMP-mediated signaling in rat insulinoma INS-1 cells. Furthermore, a C57BL/6N mice pharmacodynamics study exhibited that AGLP-1-L/HSA effectively reduced blood glucose level compared to AGLP-1/HSA.

• Journal of mucopolysaccharidosis and rare diseases
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• v.2 no.2
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• pp.35-37
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• 2016

Prader-Willi syndrome (PWS) often develops type 2 diabetes mellitus (T2DM) related to severe obesity. The prevalence of T2DM in adults with PWS (7-20%) exceeds greatly the prevalence in the general population (5-7%). It is uncommon for pre-pubertal children with PWS to develop overt diabetes or glucose intolerance. GH therapy and genotype did not influence the development of altered glucose metabolism. It has been assumed that T2DM in PWS develops as a consequence of morbid obesity and concomitant insulin resistance. However recent studies suggest the relationship between morbid obesity and T2DM development is more complex and appears to differ in PWS subjects compared to non-PWS subjects. PWS patients had relatively lower fasting insulin levels and increased adiponectin levels compared with BMI-matched obese control despite of similar levels of leptin. So PWS children may be protected to some extent form of obesity-associated insulin resistance. Although there's no data, it seems logical to approach diabetes management including weight loss and increased exercise, using similar pharmacological agents as with non-PWS obesity-related diabetes such as metformin or thiazolidinedione, with the introduction of insulin as required. On the other hand, several recent T2DM in PWS case reports suggest favorable outcomes using Glucagon-like peptide 1 (GLP-1) analog with regard to ghrelin reduction, control of glucose and appetite, weight loss and pre-prandial insulin secretion. The role of GLP-1 agonist therapy is promising, but has not yet been fully elucidated.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.6
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• pp.885-891
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• 2013

The abilities of instant gruel manufactured with colored barley and oats to improve diabetic conditions were investigated using diabetes-induced mice and rats. Mice or rats were divided into a diabetic control group and one experimental group (seven animals per group). The control groups were fed without instant gruel and experimental groups were fed basal diets supplemented with 10% instant gruel for 8 weeks. The streptozotocin (STZ)-induced diabetic rats experimental group showed a significant decrease in food intake compared to the control group. Both Type II diabetic mice and STZ-induced diabetic rats experimental groups showed higher increases in body weight than the control groups. The blood glucose levels of the experimental groups ($352{\pm}12.2$ mg/dL in Type II diabetic mice; $296.4{\pm}13.2$ mg/dL in STZ-induced diabetic rats) were lower than the untreated control groups ($426.0{\pm}15.4$ mg/dL in Type II diabetic mice; $514.0{\pm}17.6$ mg/dL in STZ-induced diabetic rats). The serum insulin levels of Type II diabetic mice increased by 38.3% in the experimental group ($12.8{\pm}1.1$ ng/mL) compared to the control group ($7.9{\pm}0.5$ ng/mL). The immunohistochemical density of insulin-secreting cells and glucagon-like peptide-1 (GLP-1)-secreting cells in the pancreas were significantly higher in the experimental groups than the control groups for Type II diabetic mice and STZ-induced diabetic rats. Therefore, we conclude that instant gruel manufactured with colored barley and oats stimulates the secretion of insulin and decreases blood sugar by activating insulin-secreting cells in the pancreatic islets of diabetic animals.

• Journal of Microbiology and Biotechnology
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• v.9 no.1
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• pp.113-118
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• 1999

The insulin-like growth factor (IGF) is found in all vertebrates and its type-II molecule is regarded as a fundamental embryonic growth factor during development. We have firstly identified, in this study, a cDNA clone corresponding to IGF-II (flIGF-II) from the adult brain of the teleost, Paralichthys olivaceus. We also examined the tissue expression of flIGF-II in several adult tissues by RT-PCR. The flIGF-II cDNA contained a complete ORF consisting of 215 amino acids and one stop codon. Its molecular characteristics appear to be similar to the previously identified IGF-II molecules, in which a common primary structure exhibiting B, C, A, D, and E domains is evidently observed. This cDNA clone seems to be cleaved at $Ala_{52}$ for the $NH_2$-end signal peptide and appears to produce a 98 amino acid-long E-peptide from the $Arg^{118}$. The functional B-D domain regions, therefore, include 65 amino acids and is able to encode a 7.4-kDa protein. The most prominent structural difference between IGF-I and IGF-II was that the D domain of IGF-II exhibits a two-codon-deleted pattern compared to the 8 amino acid-containing IGF-I. The insulin family signature in the A domain and six cysteins forming three disulfide bridges between the B and A domains were evolutionary-conserved from teleosts to mammalian IGF-II. Interestingly, the E-peptide region appears to provide a distinct hallmark between teleosts in amino acid composition. The flIGF-II shows 85.1% of sequence identity to salmon and trout, 90.6% to tilapia, and 98.4% to perch in amino acid level. In tissue expressions of IGF-II, it is very likely that flIGF-II has a significant expression in the adult brain. However, liver seems to be the main source for IGF-II production, and relatively low signals were observed in the adult muscle and kidney. Taken together, it would be concluded that the functional region for IGF-II mRNA is highly similar in phylogeny and is evolutionary, conserved as a mediator for the growth of vertebrates.

• Fisheries and Aquatic Sciences
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• v.23 no.2
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• pp.3.1-3.8
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• 2020

Background: The IGF system plays important roles in controlling growth, development, reproduction, and aging of organisms. Methods: To estimate maturation of the Pacific oyster Crassostrea gigas, we investigated the expression of insulin-like growth factor (IGF) system components and sex-specific genes. To determine the role of the IGF system in the growth and spawning period of female and male oysters, we examined mRNA expression levels of the C. gigas insulin receptor-related receptor (CIR), IGF binding protein complex acid labile subunit (IGFBP_ALS), and molluscan insulin-related peptide (MIP), as well as those of vitellogenin (Vg) and receptor-type guanylate cyclase (Gyc76C) in gonads of C. gigas collected between April and October, when sex can be determined visually in this species. Results: We found that MIP, IGFBP_ALS, and CIR mRNA expression levels were dependent on sex and month and were greater in males than in females. CIR and Vg mRNA expression levels were very similar among females, whereas IGF system components and Gyc76C were very similarly expressed among males. The highest expression values were observed in May, when oysters are mature; CIR and Vg mRNA expression levels were highest in females, and those of MIP, IGFBP_ALS, CIR, and Gyc76C were highest in males. Interestingly, we observed a 1:1 proportion of females to males during this period. Conclusion: Our results suggest that IGF system components, as well as Vg and Gyc76C, are associated with sexual maturation in C. gigas.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.34 no.5
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• pp.550-555
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• 2001

Insulin-like growth factor-I (IGF-I) is a mitogenic peptide with a molecular mass of 7 kDa. It is produced mainly in the liver and has important functions in the regulation of development and somatic growth. Moreover, Serum IGF-I concentration is regulated by the quantity and the nutritional quality of dietary protein. To determine the IGF-I level in Korean rockfish, Sabastes schlegeli, were fed four experiment diets that contained different protein quantities, namely $30\%,\;40\%,\;50\%\;and\;60\%$ for 70 days. Weight gain of the fish increased depending dietary protein quantity, Also, IGF-I concentrations increased according to dietary protein quantity, Feeding experiments were conducted to examine the effects of dietary protein sources on the serum IGF-I level in Korean rockfish, Fish meal (CO), soybean meal (SM), corn-gluten meal (CGM), meat meal (MM) and feather meal (FM) were used as variable protein sources of the formulated diet. IGF-I concentrations of the CO and MM groups ($277.7\pm23.2,\;291.5\pm41.2\;ng/mL$) were higher than those of the CGM and FM groups ($208.9\pm21.3,\;217.2\pm38.2\;ng/mL$). And IGFBP-3 levels by western blot analysis increased in good protein diets such as in the CO and MM groups. In conclusion, IGF-I may be a sensitive indicator the protein metabolism in fish as well as mammalian.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.3
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• pp.219-225
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• 2022

Glucagon like peptide-1 (GLP-1) released from enteroendocine L-cells in the intestine has incretin effects due to its ability to amplify glucose-dependent insulin secretion. Promotion of an endogenous release of GLP-1 is one of therapeutic targets for type 2 diabetes mellitus. Although the secretion of GLP-1 in response to nutrient or neural stimuli can be triggered by cytosolic Ca²⁺ elevation, the stimulus-secretion pathway is not completely understood yet. Therefore, the aim of this study was to investigate the role of reverse Na⁺/Ca²⁺ exchanger (rNCX) in Ca²⁺ entry induced by muscarinic stimulation in NCI-H716 cells, a human enteroendocrine GLP-1 secreting cell line. Intracellular Ca²⁺ was repetitively oscillated by the perfusion of carbamylcholine (CCh), a muscarinic agonist. The oscillation of cytosolic Ca²⁺ was ceased by substituting extracellular Na⁺ with Li⁺ or NMG⁺. KB-R7943, a specific rNCX blocker, completely diminished CCh-induced cytosolic Ca²⁺ oscillation. Type 1 Na⁺/Ca²⁺ exchanger (NCX₁) proteins were expressed in NCI-H716 cells. These results suggest that rNCX might play a crucial role in Ca²⁺ entry induced by cholinergic stimulation in NCI-H716 cells, a GLP-1 secreting cell line.