• Journal of Medicine and Life Science
• /
• 제21권3호
• /
• pp.62-71
• /
• 2024

The incidence of diabetes is continuously increasing worldwide, resulting in a considerable socioeconomic burden. Glycemic control using traditional diabetes medications prevents microvascular complications; however, there is no objective evidence that it prevents macrovascular complications. In the 21st century, concerns have arisen that strict glycemic control and the diabetes drug rosiglitazone might increase mortality. This led the United States Food and Drug Administration to establish guidelines that require that cardiovascular outcome trials (CVOTs) with 3-point major adverse cardiovascular events (3-P MACE) as the primary endpoints be performed for new diabetes drugs. Since then, 20 CVOTs have been reported. Dipeptidyl peptidase 4 inhibitors do not increase the incidence of cardiovascular disease; however, saxagliptin increases the risk of heart failure. Sodium-glucose cotransporter inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) not only have proven cardiovascular safety but also have shown results beyond expectations by reducing the incidence of cardiovascular diseases. Additionally, SGLT2is have been reported to markedly prevent heart failure and kidney disease. The reduction in 3-P MACE by GLP-1RAs was observed only with long-acting agents; long-acting GLP-1RAs also markedly reduced renal endpoints. However, no preventive effect against heart failure was observed with GLP-1RAs. The preventive effects of both drug types against cardiovascular and kidney diseases appear to be independent of glycemic control. In conclusion, based on CVOT results, it is necessary to actively prescribe SGLT2is and GLP-1RAs to prevent cardiovascular disease in patients with diabetes, regardless of glycemic control.

• 한국식품영양과학회지
• /
• 제42권6호
• /
• pp.885-891
• /
• 2013

유색보리와 귀리를 이용한 당뇨환자용 즉석죽의 당뇨 개선 효과를 in vivo를 통하여 확인하고 다음과 같은 결과를 얻었다. Type II 당뇨병 모델 생쥐(C57BLKS/J lar-$+Lepr^{db}/+Lepr^{db}$)의 실험종료 후 혈당의 농도는 대조군에서는 $426.0{\pm}15.4$ mg/dL이었으나, 실험군에서는 $352{\pm}12.2$ mg/dL로 약 17.4% 감소하였다. Streptozotocin으로 유발시킨 당뇨병 모델 SD계 rat의 실험종료 후 혈당의 농도는 대조군에서 $514.0{\pm}17.6$ mg/dL이었으나, 실험군에서는 $296.4{\pm}13.2$ mg/dL로 42.3% 감소하였다. Type II 당뇨병 모델 생쥐의 혈중내 인슐린 농도는 대조군에서 $7.9{\pm}0.5$ ng/mL이었으나, 실험군에서는 $12.8{\pm}1.1$ ng/mL로 약 38.3% 증가하였다. Type II 당뇨병 모델 생쥐의 췌도 내 인슐린 분비세포와 glucagon like peptide-1 분비세포에 대한 면역염색 반응은 실험군에서 대조군에 비해 췌도 내 인슐린 분비세포에 대한 면역염색 반응이 강하게 관찰되었고, streptozotocin으로 유발시킨 당뇨병 모델 SD계 rat의 췌도 내 인슐린 분비세포 및 glucagon like peptide-1 분비세포에 대한 면역염색 반응 또한 실험군에서 대조군에 비하여 인슐린 분비세포에 대한 면역염색 반응이 강하게 관찰되었다. 이상의 실험결과로 당뇨환자용 즉석죽은 당뇨병 유발 쥐들에서 췌도 내 인슐린 분비세포 기능의 활성화를 통한 인슐린의 분비를 촉진시키고, 혈당을 저하시킴을 알 수 있었다.

• Molecules and Cells
• /
• 제41권3호
• /
• pp.234-243
• /
• 2018

In recent years, the interest towards the relationship between incretins and bone has been increasing. Previous studies have suggested that glucagon-like peptide-1 (GLP-1) and its receptor agonists exert beneficial anabolic influence on skeletal metabolism, such as promoting proliferation and differentiation of osteoblasts via entero-osseous-axis. However, little is known regarding the effects of GLP-1 on osteoblast apoptosis and the underlying mechanisms involved. Thus, in the present study, we investigated the effects of liraglutide, a glucagon-like peptide-1 receptor agonist, on apoptosis of murine MC3T3-E1 osteoblastic cells. We confirmed the presence of GLP-1 receptor (GLP-1R) in MC3T3-E1 cells. Our data demonstrated that liraglutide inhibited the apoptosis of osteoblastic MC3T3-E1 cells induced by serum deprivation, as detected by Annexin V/PI and Hoechst 33258 staining and ELISA assays. Moreover, liraglutide upregulated Bcl-2 expression and downregulated Bax expression and caspase-3 activity at intermediate concentration (100 nM) for maximum effect. Further study suggested that liraglutide stimulated the phosphorylation of AKT and enhanced cAMP level, along with decreased phosphorylation of $GSK3{\beta}$, increased ${\beta}-catenin$ phosphorylation at Ser675 site and upregulated nuclear ${\beta}-catenin$ content and transcriptional activity. Pretreatment of cells with the PI3K inhibitor LY294002, PKA inhibitor H89, and siRNAs GLP-1R, ${\beta}-catenin$ abrogated the liraglutide-induced activation of cAMP, AKT, ${\beta}-catenin$, respectively. In conclusion, these findings illustrate that activation of GLP-1 receptor by liraglutide inhibits the apoptosis of osteoblastic MC3T3-E1 cells induced by serum deprivation through $cAMP/PKA/{\beta}-catenin$ and $PI3K/Akt/GSK3{\beta}$ signaling pathways.

• 한국임상약학회지
• /
• 제34권1호
• /
• pp.1-20
• /
• 2024

This review examines the pivotal clinical trials that evaluated the efficacy and safety of semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, in the management of obesity. The reported findings underscore significant and sustained weight loss achieved with semaglutide in diverse patient groups, although gastrointestinal disorders occurred frequently, leading to therapy discontinuation. Overall, the studies demonstrated the potential of semaglutide as a therapeutic option not only for type 2 diabetes but also for obesity. The treatment landscape in obesity is evolving, as reflected in changing regulatory approvals and clinical guidelines, suggesting a paradigm shift toward personalized approaches in this chronic disease states to achieve optimal treatment outcomes for patients.

• The Korean Journal of Medicine
• /
• 제99권2호
• /
• pp.78-83
• /
• 2024

Incretin-based obesity treatments are making remarkable progress, marking a new era in the field of obesity pharmacotherapy. These treatments not only meet the long-standing demands for safety and sustainability in obesity medications but also go beyond, significantly improving complications associated with obesity, such as cardiovascular diseases. This review explores the advancement in obesity treatments through the latest research findings on semaglutide and tirzepatide, two incretin-based obesity treatments currently receiving considerable attention.

• Journal of Yeungnam Medical Science
• /
• 제41권3호
• /
• pp.158-165
• /
• 2024

Over the past few decades, there has been a notable increase in the incidence of pediatric obesity, which is a significant public health concern. Children who are obese have a greater risk of type 2 diabetes, hypertension, dyslipidemia, polycystic ovary syndrome, obstructive sleep apnea, and adult obesity. Lifestyle modification therapy is typically the initial approach to treat pediatric obesity. For patients who do not achieve success with lifestyle modification therapy alone, pharmacotherapy is the next logical treatment option. When selecting an anti-obesity medication (AOM), it is essential to first ascertain the medical background of the patient, including current medications and obesity-associated comorbidities. Evaluation of obesity phenotypes in patients may also be beneficial. AOMs for pediatric obesity include metformin, orlistat, glucagon-like peptide 1 agonists, phentermine, and the phentermine/topiramate combination. Sufficient lifestyle modification therapy should be administered before considering pharmacotherapy and continued after the initiation of AOM. To ensure healthy development, monitoring growth and puberty development during anti-obesity treatments is essential.

• Journal of Ginseng Research
• /
• 제46권6호
• /
• pp.780-789
• /
• 2022

Background: Incretin impairment, characterized by insufficient secretion of L-cell-derived glucagon-like peptide-1 (GLP-1), is a defining step of type 2 diabetes mellitus (T2DM). Ginsenoside compound K (CK) can stimulate GLP-1 secretion; however, the potential mechanism underlying this effect has not been established. Methods: CK (40 mg/kg) was administered orally to male db/db mice for 4 weeks. The body weight, oral glucose tolerance, GLP-1 secretion, gut microbiota sequencing, bile acid (BA) profiles, and BA synthesis markers of each subject were then analyzed. Moreover, TGR5 expression was evaluated by immunoblotting and immunofluorescence, and L-cell lineage markers involved in L-cell abundance were analyzed. Results: CK ameliorated obesity and impaired glucose tolerance in db/db mice by altering the gut microbiota, especially Ruminococcaceae family, and this changed microbe was positively correlated with secondary BA synthesis. Additionally, CK treatment resulted in the up-regulation of CYP7B1 and CYP27A1 and the down-regulation of CYP8B1, thereby shifting BA biosynthesis from the classical pathway to the alternative pathway. CK altered the BA pool by mainly increasing LCA and DCA. Furthermore, CK induced L-cell number expansion leading to enhanced GLP-1 release through TGR5 activation. These increases were supported by the upregulation of genes governing GLP-1 secretion and L-cell differentiation. Conclusions: The results indicate that CK improves glucose homeostasis by increasing L-cell numbers, which enhances GLP-1 release through a mechanism partially mediated by the gut microbiota-BA-TGR5 pathway. Therefore, that therapeutic attempts with CK might be useful for patients with T2DM.

• Journal of mucopolysaccharidosis and rare diseases
• /
• 제2권2호
• /
• pp.35-37
• /
• 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 mucopolysaccharidosis and rare diseases
• /
• 제2권2호
• /
• pp.50-51
• /
• 2016

Combining basal insulin therapy with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) has clear clinical advantages, and is supported by the latest EASD/ADA position statement (1). IDegLira is a once-daily combination of the basal insulin, degludec, and the GLP-1RA, liraglutide, in one pen. The DUAL phase 3 clinical trial program provides important evidence about the efficacy and safety of IDegLira in three different populations of patients with type 2 diabetes (T2D): insulin naïve subjects uncontrolled on oral antidiabetic drugs (OADs), subjects uncontrolled on OAD(s) and a GLP-1 RA, and subjects uncontrolled on OAD(s) and basal insulin. Treatment with IDegLira reduced mean HbA1c to below the EASD/ADA treatment target of 7.0% in all five trials. The mean reduction of HbA1c from baseline ranged from 1.3% and 1.9%. IDegLira resulted in weight loss for subjects uncontrolled on basal insulin, was weight neutral for subjects on OADs and weight gain was minimal (2 kg) for subjects previously treated with a GLP-1 RA. Rates of hypoglycaemia were low across all the trials, particularly considering the level of glycaemic control achieved.

• 한국미생물·생명공학회지
• /
• 제40권3호
• /
• pp.180-185
• /
• 2012

Type 2 Diabetes Mellitus, a chronic metabolic disorder which results from a high blood glucose level, is one of the most prevalent and costly diseases of our time. Considering increasing rates of obesity and the aging population in Korea, the number of diabetic patients is likely to rise rapidly in the future. There are five conventional diabetic drugs which work through different mechanisms; sulfonylureas, biguanide, meglitinide, alpha-glucosidase inhibitors, and thiazolidinedione. Although they all have antidiabetic effects, some side effects such as hypoglycemia, weight gain and gastrointestinal intolerance are associated with them. Incretin based therapies, utilizing glucagon-like peptide-1 (GLP-1) and dipeptidyl peptidase-4 (DPP-4) inhibitors, which have a lower risk of adverse side effects, have recently been introduced. At present PPAR-targeting drugs are being actively developed. In this research review, particular emphasis has been placed on the current trends and possible biological targets for the new generation of antidiabetic drugs.