• Applied Microscopy
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• v.37 no.4
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• pp.249-258
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• 2007

The Pancreatic islet are the clusters of endocrine cells scattered through out the exocrine pancreas. Transplantation of a sufficient pancreatic islets can normalize blood glucose level so that may prevent devastating complications of type I diabetes(IDDM) and other side effects of the IDDM. Recently, there are several approaches to transplant sufficient pancreatic islet, and it was comprised in increase or regeneration of the endogenous $\beta$-cell mass from donor's pancreas, but relatively few studies have been devoted to the morphological characters of the isolated and 3 day cultured pancreatic islets. We investigated morphological pattern of intracellular structure of isolated and 3 day cultured pancreatic islets. The morphological characters of the pancreatic islets were observed by scanning electron microscope and transmission electron microscope, and insulin distribution of the each islets were observed by transmission electron microscope, and were labeled with insulin antibody. Intracellular structures including nuclei, mitochondria, RER, Golgi complex and many secretory granules were normally appeared in the isolated pancreatic islets which was extracted immediately dornor's pancreas, however, There is a significant morphological changes between the 3 day cultured pancreatic islets and isolated islets. 3 day cultured pancreatic islet's $\beta$-cells had normal nuclei but increased cytoplasm mass and RER and developed Golgi complex. Insulin secretory granules were decreased in numbers rather than isolated pancreatic islet. In this study, the pattern of intracellular structure variation was examined during pancreatic islet culture. Most distinct features are variation of the insulin secretory granules, and developed RER, and dilated golgi complex. Therefore, we suggested that the various change of the morphological characters on cultured pancreatic islets were responsible for the function(biosynthesis and secretion of insulin) and growth. These results were also cultured islets have greater ability to recover and maintain normoglycemia than isolated islet transplantation.

• Asian-Australasian Journal of Animal Sciences
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• v.16 no.7
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• pp.1060-1065
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• 2003

To determine whether dietary fatty acids affect pancreatic $\beta$-cell function, the INS-1 $\beta$-cells and the pancreatic islets isolated from Zucker obese (fa/fa) rats were cultured with stearic acid and conjugated linoleic acid (CLA). As a result, DNA fragmentation laddering was substantially decreased in the INS-1 $\beta$-cells and the isolated pancreatic islets cultured with 2 mM CLA compared to those cultured with stearic acid. To investigate the mechanism by which CLA alleviates cell apoptosis under DNA fragmentation assay, we examined mRNA expressions of apoptosis-related proteins including Bax and Bcl-2 associated with cell death agonist and antagonist, respectively, in both INS-1 cells and islets cultured with 2 mM fatty acids. Bax mRNA expression was not altered by either stearic acid or CLA, whereas Bcl-2 mRNA expression was enhanced by CLA when compared to the stearic acid cultures. However, there were no changes in cell apoptosis and apoptotic-regulating gene products in either INS-1 cells or isolated islets treated with or without 2 mM CLA. It is concluded that CLA maintains $\beta$-cell viability via increased Bcl-2 expression compared to the stearic acid cultures, which may help to alleviate, at least somewhat, the onset of NIDDM in the physiological status. More detailed study is still needed to elucidate the effect of CLA on the prevention of fatty acid-induced $\beta$-cell apoptosis.

• YAKHAK HOEJI
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• v.42 no.4
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• pp.408-413
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• 1998

To establish prediabetes in vitro/ model concerning the etiology of Insulin Dependent Diabetes Mellitus (IDDM) in cellular level we have designed experimental prediabefic model in pancreatic beta cells. RINm5F, HIT-T15 and isolated rat islets were chosen as pancreatic beta cells. Since interleukin-$1{\beta}$-induced beta cell cytotoxicity has been implicated in the autoimmune cytotoxicity of IDDM, we used inteleukin-$1{\beta}$ as diabetogenic agent. For establishment of prediabetic in vitro model, the degree of beta cell deterioration was determined by cell proliferation, insulin release and morphological appearance. Cell proliferation, insulin release and morphology were changed dose-dependently in condition that inteleuldn-$1{\beta}$ was exposured to pancreatic beta cells. The concentration and exposure time of interleukin-$1{\beta}$ to set up prediabetic model in beta cell lines and isolated rat islets were 100${\sim}$1000U/ml, 48hr. And 25${\sim}$100U/ml, 48hr, respectively.

• YAKHAK HOEJI
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• v.41 no.2
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• pp.260-267
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• 1997

To establish prediabetes in vitro model concerning the etiology of IDDM(Insulin Dependent Diabetes Mellitus) in cellular level we have designed prediabetes in vitro models in pa ncreatic beta cells. HIT-T15, RINm5F and isolated rat islets were chosen as pancreatic beta cells, and streptozotocin (STZ) used as diabetogenic agent. Degree of beta cell destruction to establish prediabetic in vitro model was determined by cell proliferation and insulin release using thymidine uptake and radio immuno assay. When HIT-T15 and RINm5F cells were treated with STZ, the degree of cell deterioration was dependent upon the origin and passage number of beta cells, and in the case of isolated islets STZ showed the more sensitivity than above two beta cell lines. The concentration and exposure time of STZ treatment to establish prediabetes in vitro model in beta cell lines and isolated rat islets were 2 ~ 10mM, 30 min. and 1 ~ 5mM, 30 min., respectively.

• Journal of Microbiology and Biotechnology
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• v.32 no.12
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• pp.1615-1621
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• 2022

Tissue regeneration is the ultimate treatment for many degenerative diseases, however, repair and regeneration of damaged organs or tissues remains a challenge. Previously, we showed that B1 Ab and H3 Ab induce stem cells to differentiate into microglia and brown adipocyte-like cells, while trafficking to the brain and heart, respectively. Here, we present data showing that another selected agonist antibody, P1 antibody, induces the migration of cells to the pancreatic islets and differentiates human stem cells into beta-like cells. Interestingly, our results suggest the purified P1 Ab induces beta-like cells from fresh, human CD34⁺ hematopoietic stem cells and mouse bone marrow. In addition, stem cells with P1 Ab bound to expressed periostin (POSTN), an extracellular matrix protein that regulates tissue remodeling, selectively migrate to mouse pancreatic islets. Thus, these results confirm that our in vivo selection system can be used to identify antibodies from our library which are capable of inducing stem cell differentiation and cell migration to select tissues for the purpose of regenerating and remodeling damaged organ systems.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.5
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• pp.261-266
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• 2003

Type 1 diabetes is an organ-specific autoimmune disease caused by the cytotoxic T cells-mediated destruction of the insulin-producing beta cells in the Langerhans pancreatic islets. Hepatocyte growth factor (HGF) is a potent mitogen and a promoter of proliferation of insulin producing beta cells of pancreatic islets. To study the role of HGF via viral vector in the development of streptozotocin (STZ)-induced diabetes in mice, we have developed an adenoviral vector genetically engineered to carry the gene for human HGF (hHGF) and evaluate the change of blood glucose, insulin level, and insulin-secreting beta cells of pancreatic islets. We demonstrate that the treatment with hHGF gene prevented the development of STZ-induced diabetes and increased serum insulin level to above normal range. Furthermore, it preserved pancreatic beta cells from destruction. These in vivo results may support previous findings that HGF is insulinotropic agent for beta cells and HGF treatment renders the cells to be resistant to the development of diabetes from STZ administration. We suggest that an adenoviral mediated hHGF gene therapy is a good candidate for the prevention and treatment of type 1 diabetes.

• Applied Microscopy
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• v.31 no.3
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• pp.267-274
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• 2001

This study was carried out to understand the effects of Saengchinyanghyoltang-gamibang (SGT) on pancreatic islets of the mice induced with streptozotocin (STZ). In the control group, two times injected with 50 mg/kg 572 at 24-hour intervals, a few number of insulin immunoreactive-cells are observed at the pancreatic islets of the mice. In the experimental group which administered with extract of SGT during 21-day, a number of immunoreactive-cells are observed at the pancreatic islets. According to the electron microscopic observation, $\beta-cells$ of the control group were contained a few of secretory granules, but also these granules were contained electro-lucent materials. In the experimental group, a lot o( secretory granules and well developed cell organelles are observed at the $\beta-cells$. The level of glucose was significantly decreased in the experimental group compared with control group, but the level of BUN was similar in these two groups. These results suggest that administration of SGT to the mice improved the damage of $\beta-cells$ from injected with STZ.

• Archives of Pharmacal Research
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• v.26 no.7
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• pp.559-563
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• 2003

Cytokines produced by immune cells infiltrating pancreatic islets have been incriminated as important mediators of $\beta$-cell destruction in insulin-dependent diabetes mellitus. In non insulin-dependent diabetes, cytokines are also associated with impaired $\beta$-cell function in high glucose condition. By the screening of various natural products blocking $\beta$-cell destruction, we have recently found that epigallocatechin gallate (EGCG) can prevent the in vitro destruction of RINm5F cell, an insulinoma cell line, that is induced by cytokines. In that study we suggested that EGCG could prevent cytokine-induced $\beta$-cell destruction by down-regulation of nitric oxide synthase (NOS) through inhibition of NF-kB activation. Here, to verify the in vivo antidiabetogenic effect of EGCG, we examined the possibility that EGCG could also prevent the experimental autoimmune diabetes induced by the treatment of multiple low doses of streptozotocin (MLD-STZ), which is recognized as an inducer of type I autoimmune diabetes. Administration of EGCG (100 mg/day/kg for 10 days) during the MLD-STZ induction of diabetes reduced the increase of blood glucose levels caused by MLD-STZ. Ex vivo analysis of $\beta$-islets showed that EGCG downregulates the MLD-STZ-induced expression of inducible NOS (iNOS). In addition, morphological examination showed that EGCG treatment ameliorated the decrease of islet mass induced by MLD-STZ. In combination these results suggest that EGCG could prevent the onset of MLD-STZ-induced diabetes by protecting pancreatic islets. Our results therefore revealed the possible therapeutic value of EGCG for the prevention of diabetes mellitus progression.

• Journal of the East Asian Society of Dietary Life
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• v.22 no.3
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• pp.334-340
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• 2012

This study was carried out to investigate the effects of Opuntia ficus-indica complex (OF) on blood glucose, glucose tolerance, plasma insulin level and histopathological appearance of pancreatic islets in streptozotoxin (STZ)-induced diabetic rats. Thirty-two male Sprague-Daweley rats were divided into non-diabetic control (NC), diabetic control (DC), diabetic OF of 2% (OF-2) and diabetic OF of 5% (OF-5) and fed experimental diets for 3 weeks. Compared to the DC group fasting blood glucose levels in the OF-2 and OF-5 groups were significantly (p<0.05) reduced while fasting plasma insulin level in the OF-2 and OF-5 groups were significantly (p<0.05) increased. Glucose tolerance in the OF-2 and OF-5 groups were improved. Histopathological observation of pancreatic islets of the OF-2 and OF-5 groups showed hyperplasia which was very similar to NC. Numbers of ${\beta}$-cells in OF-2 ($47.81{\pm}0.92$) and OF-5 ($81.64{\pm}2.80$) were higher than numbers of ${\beta}$-cells in DC ($13.18{\pm}1.01$). These results imply that the intake of OF improves ${\beta}$-cell proliferation and prevents the death of ${\beta}$-cells in STZ-induced diabetic rats.

• Journal of Microbiology and Biotechnology
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• v.9 no.2
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• pp.150-156
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• 1999

The induction of proliferation of adult rat islets was investigated under various culture conditions. The islets were isolated from male Sprague-Dawley rats and subsequently embedded in collagen gels, which mimic the in vivo three-dimensional surroundings. During the culture period, the effects of heterologous serum (fetal bovine serum, FBS), epidermal growth factor (EGF), and retinoic acid (RA) on islet growth were examined with respect to the morphological and total DNA content changes. To investigate these changes at the cellular level, whole mount immunocytochemistry using specific antibodies for insulin and glucagon was performed. The results showed that (i) collagen gels as an extracellular matrix can maintain islets in a similar way to that in vivo, (ii) heterologous serum (FBS) had stimulatory effects on islet proliferation in a dose-dependent manner, (iii) RA had inhibitory effects on islet proliferation induced by the serum in a dose-dependent manner, (iv) EGF had weak inhibitory effects on islet proliferation induced by the serum except at the concentration of 10 nM where its effect was not significant, and (v) whole mount immunocytochemistry revealed that newly proliferated islet cells were mainly $\beta$-and $\alpha$-cells.