• Fisheries and Aquatic Sciences
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• 제27권1호
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• pp.17-22
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• 2024

Diabetes Mellitus (DM) is a major health issue increasing worldwide. Currently, nearby half a billion people have diabetes. Two major types of DM that type 1 and type 2-DM have different etiologies but feature a crucial common pathological transition into dysfunction of pancreatic β-cells and consequently leading hyperglycemia and finally go into DM. Therefore, maintaining of β-cells such as preventing β-cells degeneration, and promoting β-cells regeneration and proliferation will be essential approaches in prevention and/or treatment of DM. There are many reports that various types of seaweed control metabolic diseases such as obesity, high blood pressure, and blood sugar control. However, no new drug candidates have been developed yet. Additionally, although seaweed has excellent blood sugar control effects, there is no evidence that it directly proliferates or regenerates beta cells. Therefore, we studied on the promotion of β-cell regeneration by a seaweed, Polysiponia morrowii extract (PME) which preserves β-cells and maintains its function. As a result, it was confirmed that PME directly promotes the proliferation of pancreatic islet β-cells with insulin secretion function in in vivo. Therefore, PME shows potential as a candidate for β-cell regeneration that may play a fundamental role in the treatment of diabetes.

• Preventive Nutrition and Food Science
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• 제9권4호
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• pp.367-373
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• 2004

The prevalence of type-2 diabetes increases remarkably in post-menopausal women, possibly because insulin secretion fails to compensate for the insulin resistance induced in various tissues by estrogen insufficiency. However, this has not been fully defined. Therefore, the present study investigated whether an ovariectomy (OVX) would increase insulin resistance and decrease the $\beta$-cell function and mass in female rats with and without a $90\%$ pancreatectomy (Px). Female rats aged 15 weeks were divided into four groups: 1) OVX + Px, 2) SOVX (sham operation of OVX) + Px, 3) OVX + SPx (sham operation of Px), and 4) SOVX + SPx, and given a $30\%$ fat diet for 8 weeks. At the end of the experimental period, the islet function and insulin resistance were determined using a hyperglycemic clamp and a euglycemic hyperinsulinemic clamp, respectively. The OVX only increased the body weight in the SPx rats, which was partially related to the food intake. Yet, the OVX did increase the peripheral insulin resistance, while the Px increased this resistance further. The OVX and Px both exacerbated the islet function, as measured by the insulin secretion pattern, while delaying and decreasing the first-phase insulin secretion. The OVX only decreased the proliferation of $\beta$-cells in the Px rats, while increasing apoptosis in both the Px and SPx rats. As a result, the OVX decreased the $\beta$-cell mass in the Px rats, but increased the mass in the SPx rats. In conclusion, an OVX was found to accelerate the development and progression of diabetes by increasing the insulin resistance and decreasing the $\beta$-cell mass. Therefore, menopause can be a risk factor for type-2 diabetes, mainly due to a deceased proliferation of $\beta$-cells.

• BMB Reports
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• 제52권5호
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• pp.295-303
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• 2019

Breakthroughs in stem cell technology have contributed to disease modeling and drug screening via organoid technology. Organoid are defined as three-dimensional cellular aggregations derived from adult tissues or stem cells. They recapitulate the intricate pattern and functionality of the original tissue. Insulin is secreted mainly by the pancreatic ${\beta}$ cells. Large-scale production of insulin-secreting ${\beta}$ cells is crucial for diabetes therapy. Here, we provide a brief overview of organoids and focus on recent advances in protocols for the generation of pancreatic islet organoids from pancreatic tissue or pluripotent stem cells for insulin secretion. The feasibility and limitations of organoid cultures derived from stem cells for insulin production will be described. As the pancreas and gut share the same embryological origin and produce insulin, we will also discuss the possible application of gut organoids for diabetes therapy. Better understanding of the challenges associated with the current protocols for organoid culture facilitates development of scalable organoid cultures for applications in biomedicine.

• IMMUNE NETWORK
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• 제16권5호
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• pp.281-285
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• 2016

CD4⁺ regulatory T cells (Tregs) are essential for normal immune surveillance, and their dysfunction can lead to the development of autoimmune diseases, such as type-1 diabetes (T1D). T1D is a T cell-mediated autoimmune disease characterized by islet b cell destruction, hypoinsulinemia, and severely altered glucose homeostasis. Tregs play a critical role in the development of T1D and participate in peripheral tolerance. Pluripotent stem cells (PSCs) can be utilized to obtain a renewable source of healthy Tregs to treat T1D as they have the ability to produce almost all cell types in the body, including Tregs. However, the right conditions for the development of antigen (Ag)-specific Tregs from PSCs (i.e., PSC-Tregs) remain undefined, especially molecular mechanisms that direct differentiation of such Tregs. Auto Ag-specific PSC-Tregs can be programmed to be tissue-associated and infiltrate to local inflamed tissue (e.g., islets) to suppress autoimmune responses after adoptive transfer, thereby avoiding potential overall immunosuppression from non-specific Tregs. Developing auto Ag-specific PSC-Tregs can reduce overall immunosuppression after adoptive transfer by accumulating inflamed islets, which drives forward the use of therapeutic PSC-Tregs for cell-based therapies in T1D.

• 대한수의학회지
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• 제37권2호
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• pp.253-262
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• 1997

To investigate morphological changes in the endocrine pancreas of chicken after pancreatic duct ligation, experimental animals were subdivided to control, 12 hours, 1 day, 2 days, 4 days, 7 days and 10 days groupes and all of three pancreatic ducts of chicken were ligated by surgical procedure and then the morphological changes were observed. In pancreatic islets, the vacuolation and invasion of connective tissue were occurred in all experimental groups and dissociation of pancreatic islets was detected in 4 days after pancreatic duct ligation and hold out to 10 days. The peak of the morphological changes in pancreatic islets was detected in 4 days after pancreatic duct ligation. In the results of immunohistochemical methods against glucagon, insulin, somatostatin and bovine pancreatic polypeptide(BPP), the number of immunoreactive pancreatic islets were decreased but the size increased with time, so the number of immunoreactive cells in each pancreatic islets were increased. Glucagon-immunoreactive cells were not changed but insulin-immunoreactive cells were decreased with time(p<0.05). BPP-immunoreactive cells were increased in 2 days after pancreatic duct ligation and then decreased with time(p<0.05). Somatostatin-immunoreactive cells were increased with time(p<0.05) in dark islets.

• 대한세포병리학회지
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• 제3권1호
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• pp.19-24
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• 1992

A case of paraganglioma of the retroperitoneum diagnosed by fine needle aspiration cytology is described. A 60-year-old man presented with abdominal discomfort for 4 months. The smear revealed cellular sheets with partly rosettoid appearance. Many piexiform capillaries were distributed between the cellular sheets or encircled the cellular nests forming zell-ballen pattern. The tumor cells were monotonous and oval to round. The cytoplasm was amphophillc, finely granular and poorly defined. The nuclei were round and had evenly dispersed chromatin and small nucleoli. Cells having large or spindle nuclei were some-times observed. The tissue sections showed typical findings of paragnglima. The cytological differential diagnoses included islet cell tumor of the pancreas and carcinold tumor. The clinical and histoloigic findings as well as cytologic findings were helpful to confirm the diagnosis.

• Journal of Pharmaceutical Investigation
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• 제16권3호
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• pp.89-100
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• 1986

Although insulin has been available for the treatment of diabetes mellitus for more than half a centry, the deficiency of conventional insulin therapy for diabetic patients have, to this date, not been satisfactorily overcome by any method. The development of potential delivery systems for insulin is highly important to prevent excessive fluctuation of plasma glucose levels, which results in long term complications in the diabetic. There are three major approaches toward development of glucose responding insulin delivery systems: A bioengineering approach is to devise mechanical components capable of releasing insulin in amounts appropriate to varying blood-glucose requirements. A biological approach relies upon cultured, living pancreatic beta cells encapsulated to constitute an insulin delivery unit. A biochemical approach is to synthesize a stable and biologically active glycosylated insulin that is complementary to the binding sites of lectin. This paper will cover several specific areas, including pancreatic transplantation(total or isolated islet cells), artificial pancreases(bioengineering or biological approach), controlled delivery system, glucose sensitive membrane systems, and a self-regulating insulin delivery system.

• 한국발생생물학회:학술대회논문집
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• 한국발생생물학회 2003년도 제3회 국제심포지움 및 학술대회
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• pp.60-60
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• 2003

Embryonic stem (ES) cells have property of self-renewal and can differentiate into the cells of all three primary germ layers. Recently, many growth factors, alteration of culture condition and gene modifications have been used to differentiate mouse and human ES cells into specific cell types. This study was performed to evaluate the differentiation protocol for human ES cells to the endodermal lineage cells. Human ES cells (Miz-hESl ) were cultured on STO feeder layer mitotically inactivated with mitemycin C, and embryoid bodies (EBs) were formed by suspension culture. Differentiation protocol of EBs consisted of three steps: stage I, culture of EBs for 6 days with ITSFn medium; stage II, culture of stage I cells for 8 days with N2 medium ; stage III, culture of stage II cells for 22 days with N2 medium. mRNA levels of the endodermal lineage differentiation genes were analyzed by semi- quantitative RT-PCR. The Oct-4 expression, a marker of the pluripotent state, was detected in undifferentiated human ES cells but progressively decreased after EBs formation. Differentiating human ES cells expressed marker genes of endodermal differentiation and pancreatic islet cells. GATA4, a-fetoprotein, Glut-2, and Ngn3 were expressed in all stages. However, albumin and insulin were expressed in only stage III cells. The human ES cells can be differentiated into endodermal lineage cells by multiple step culture system using various supplements. We are developing the more effective protocols for guided differentiation of human ES cells.

• Molecules and Cells
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• 제41권10호
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• pp.909-916
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• 2018

In pancreatic ${\beta}$ cells, glucose stimulates the biosynthesis of insulin at transcriptional and post-transcriptional levels. The RNA-binding protein, polypyrimidine tract-binding protein 1 (PTBP1), also named hnRNP I, acts as a critical mediator of insulin biosynthesis through binding to the pyrimidine-rich region in the 3'-untranslated region (UTR) of insulin mRNA. However, the underlying mechanism that regulates its expression in ${\beta}$ cells is unclear. Here, we report that glucose induces the expression of PTBP1 via the insulin receptor (IR) signaling pathway in ${\beta}$ cells. PTBP1 is present in ${\beta}$ cells of both mouse and monkey, where its levels are increased by glucose and insulin, but not by insulin-like growth factor 1. PTBP1 levels in immortalized ${\beta}$ cells established from wild-type (${\beta}IRWT$) mice are higher than levels in ${\beta}$ cells established from IR-null (${\beta}IRKO$) mice, and ectopic re-expression of IR-WT in ${\beta}IRKO$ cells restored PTBP1 levels. However, PTBP1 levels were not altered in ${\beta}IRKO$ cells transfected with IR-3YA, in which the Tyr1158/1162/1163 residues are substituted with Ala. Consistently, treatment with glucose or insulin elevated PTBP1 levels in ${\beta}IRWT$ cells, but not in ${\beta}IRKO$ cells. In addition, silencing Akt significantly lowered PTBP1 levels. Thus, our results identify insulin as a pivotal mediator of glucose-induced PTBP1 expression in pancreatic ${\beta}$ cells.

• 대한수의학회지
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• 제33권3호
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• pp.369-379
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• 1993

북극여우의 위장췌 내분비세포의 부위별 분포, 출현빈도 및 세포의 종류를 밝히고자 면역조직화학적으로 관찰하였던 바 위장관에서는 6종, 췌장에서는 4종의 면역반응세포가 동정되었다. 5-HT 및 somatostatin면역반응세포는 전 위장관에 다수 분포하였으나 이중 somatostatin 면역반응세포는 장관에서 소수로 관찰되었다. Gas/CCK 면역반응세포는 주로 유문부와 십이지장에 국한하여 다수 분포하였다. Glucagon 면역반응세포를 분문부와 위저부에서 다수 그리고 장관에서 소수 관찰되었다. BPP 면역반응세포는 분문부와 위저부에 중등도, 대장에 소수 분포하였다. 다수의 porcine CG 면역반응세포가 분문부와 위저부에서만 동정되었다. 한편 췌장에서는 somatostatin, glucagon, BPP 및 insulin 등 4종의 면역반응세포가 췌도 및 외분비부에서 관찰되었다. 이상의 결과는 위췌장 내분비세포의 부위별 분포와 출현빈도가 동물종에 따라 매우 상이하다는 사실을 시사한다.