Skip Navigation
Skip to contents

Diabetes Metab J : Diabetes & Metabolism Journal

Search
OPEN ACCESS

Search

Page Path
HOME > Search
4 "Beta cell mass"
Filter
Filter
Article category
Keywords
Publication year
Authors
Original Articles
The Effect of Long-term Treatment of Ramipril on Glucose Tolerance and Pancreatic Islets in Type 2 Diabetes Animal Model (OLETF Rats).
Seung Hyun Ko, Kun Ho Yoon, Myung Mi Kim, Yu Bae Ahn, Ki Ho Song, Soon Jib Yoo, Hyun Shik Son, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 2001;25(6):469-482.   Published online December 1, 2001
  • 1,145 View
  • 30 Download
AbstractAbstract PDF
BACKGROUND
In a Heart Outcomes Prevention Evaluation HOPE study, ramipril, a long- acting angiotensin-converting enzyme (ACE) inhibitor, significantly reduced the death rates the number of myocardial infarctions, strokes, heart failure as well as the risk of complications related to diabetes and of diabetes itself. However, it is known that ACE inhibitors improve glucose tolerance or insulin sensitivity or reduce the incidence of diabetes. METHODS: 24 week-old OLETF (Otsuka Long Evans Tokushima Fatty) rats weighing 400~450 g were used in this study. 4 groups of rats were examined in parallel for 40 weeks. The OLETF rats were randomized for treatment with an aqueous solution of ramipril ( 5mg/Kg) daily [OL (RMP), n=10)] and with saline [OL(CON), n=10)]. The LETO rats were also randomized in the same was as the OLETF rats (LT (RMP), n=10, LT (CON), n=10). The blood glucose level, body weight, systolic and diastolic blood pressure was assessed every month. At 3 and 6 months, the 24hrs urinary protein concentration was measured, and as insulin tolerance test and oral glucose tolerance test were conducted in all experimental groups. After 6 months, the body weight was matched for 2 months in each corresponding group. Subsequently, a 15% sucrose loading was done for 2 months. After the glucose tolerance test, the pancreas was excised and immunohistochemical staining was conducted for insulin to quantify the beta cell mass by a point-counting method. In addition, the islet morphology was evaluated in the pancreas. RESULTS: Ramipril treatment for a period of 6 months improved the 2hr blood glucose level, the area under the glucose curve in the oral glucose tolerance test, insulin sensitivity in addition to lowering significantly systolic and diastolic blood pressure and 24hrs urinary protein level significantly in OLETF rats. Of note, a lower weight gain was observed in both the ramipril-treated animals at 6 months. After weight matching, the AUCg and 2hr blood glucose level values were similar between the corresponding groups, but a 15% sucrose loading worsened the AUCg value. Histologically, the islets were less disorganized and the extent of fibrosis was lower in the ramipril- treated OLETF rats in the trichrome stain. CONCLUSION: Long-term treatment of ramipril, a long acting angiotensin-converting enzyme inhibitor may be useful for suppressing weight gain and proteinuria in addition to having aprotective effect on the islet to harmful stimuli such as hyperglycemia.
The Changes of Beta Cell Mass and Islet Morphology in OLETF (Otsuka Long Evans Tokushima Fatty) Rats After Partial Pancreatectomy .
Seung Hyun Ko, Kun Ho Yoon, Sun Hee Suh, Yu Bae Ahn, Soon Jib Yoo, Ki Ho Song, Hyun Shik Son, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 2001;25(1):50-62.   Published online February 1, 2001
  • 1,154 View
  • 20 Download
AbstractAbstract PDF
BACKGROUND
Insulin resistance and incomplete beta cell compensation play a major role for development of type 2 diabetes. When insulin resistance were induced by any cause, appropriate beta-cell proliferation is a key factor for maintaining the normal glucose metabolism. Compensatory beta-cell proliferation for adapting to increased insulin resistance might be achieved by neogenesis of beta-cell from duct cells, replication of preexisting beta-cells and also inhibition of beta-cell apoptosis. Previously incomplete beta-cell compensation was observed in OLETF rat, animal model of type 2 diabetes, after partial pancreatectomy, but there were no reports about the underlying pathogenesis. Therefore, this study was designed to study on the mechanism of incomplete beta-cell compensation in OLETF rat after partial pancreatectomy especially focus on beta-cell proliferation. METHODS: 12 week-old OLETF (Otsuka Long Evans Tokushima Fatty) rats weighing 280-320 g were used. 80% partial pancreatectomy was done. Experimental animals were divided into the 4 subgroups by date of killing after surgery: 0, 3, 90 days. After glucose tolerance test, pancreas remnant was excised and immunohistochemical staining was done for insulin to quantify the beta cell mass by point-counting method and also observed the amount of fibrosis of the islets after Masson's trichrome staining of the pancreas. RESULTS: We observed that impaired glucose tolerance or diabetes were developed after 80% pancreatectomy. We observed rapidly proliferating duct cells in the adjacent area of common pancreatic duct and main duct even up to 90 days after partial pancreatectomy. In OLETF rats, beta cell mass was not increased enough compared to LETO rats and some destructive features of islet architectures were noted at 90 days after pancreatectomy. CONCLUSION: The changes of beta cell mass seems to be a dynamic process adjusting to metabolic demand. Severe hyperglycemia and islet disorganization were apparent in OLETF rats despite of existence of beta cell regeneration and renewal process. So it seemed that hyperglycemia accelerated aging process or senescence of beta cells in OLETF rats.
The Effect of Increased Beta Cell Mass on Glucose Tolerance in Rat.
Eun Sook Oh, Kun Ho Yoon, Sun Hee Seo, Sook Young Lee, Seung Hyun Ko, Won Young Lee, Sung Rae Kim, Moo Il Kang, Bong Yon Cha, Kwang Woo Lee, Ho Young Son, Sung Goo Kang
Korean Diabetes J. 2000;24(6):629-640.   Published online January 1, 2001
  • 1,262 View
  • 23 Download
AbstractAbstract PDF
BACKGROUND
The aim of the present study is to evaluate the effect of increased beta cell mass by continuous 96-hour 50% glucose infusion on glucose tolerance in insulin resistance state induced by high fat diet in normal Sprague-Dawley rats. METHODS: The adult Sprague-Dawley rats weighing 200-250 gm were infused with 50% glucose or 0.45% saline via external jugular vein catheter for 96 hours. The both groups of rats were then randomly stratified into the two subgroups, and fed either high fat diet (54% of energy from fat) or normal rat chow (8.6% of energy from fat) for 4 weeks. On day 28, blood was collected for measuring the serum concentration of insulin, and oral glucose tolerance test (2 gm/kg body weight) was performed after overnight fasting. The beta cell mass was counted with the morphometric point-counting technique of Weibel. RESULTS: After the 96 hour infusion, the percentage of beta cell mass was significantly increased in glucose-infused rats when compared to the saline-infused group (p=0.03) and maintained up to day 28. Body weight gains were significantly greater in glucose infused rats than those of saline infused group (Increased value of weight : 142.9+/-15.2 g in glucose infused rats vs 125.3+/-21.1 g in saline infused rats, p=0.01). In the saline infusion-high fat diet group, the number of rats with impaired glucose tolerance was higher than those of other group (p<0.005). The glucose values at 90 minute and 120 minute were higher in saline infusion-high fat diet group than in glucose infusion-high fat diet group (p< 0.05). CONCLUSION: Our findings suggest that the increased beta cell mass has a favorable effect on glucose tolerance in insulin resistance state which were evoked by high fat diet.
Quantification of the Pancreatic -cell Mass in Normal and Type 2 Diabetic Subjects in Korea.
Kun Ho Yoon, Seung Hyun Ko, Jung Min Lee, Sung Rae Kim, Sun Hee Seo, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Yong Gui Kim, In Sung Moon, Myung Deuk Lee, Dong Ku Kim, Kyo Young Lee, Chan Suk Kang, Byung Ki Kim
Korean Diabetes J. 2000;24(5):524-532.   Published online January 1, 2001
  • 1,552 View
  • 18 Download
AbstractAbstract
BACKGROUND
There have been several reports about insulin secretory impairment in non-obese type 2 diabetic patients and even in impaired glucose tolerant subjects in Korea. Insulin secretory impairment might be induced by insufficient beta-cell mass, functional defects of beta-cells or both. To clarify the cause of impaired insulin secretion in type 2 non-obese diabetic patients in Korea, beta- cell masses were quantified in normal and type 2 diabetic subjects. METHOD: Normal pancreases were procured by 6 heart-beating non-diabetic donors under informed consent from relatives and approval of the university ethical committee. To quantify the beta cell mass and insulin content in various part of the pancreas, first we divided it into 3 parts: head, body and tail, and then each three parts were weighed and subdivided again into 8 segments equally. For diabetic patients, tissue sections were obtained from 15 partial or total pancreatectomized type 2 diabetic patients of any causes. After being fixed, tissues were immunostained using the Streptavidin-biotin-peroxidase method with anti-insulin antibody. Beta cells were counted by point count method. RESULTS: The mean value of total pancreas weight of normal subjects (n=6) was 77.1+/-14.6 g, that of mean relative volume of beta cells in the pancreas was 2.1+/- 0.9%, ranging from 1.4% to 3.1% (head 2.3+/-0.6%, body 1.8+/-0.2%, tail 2.2+/-0.4%). Mean value of total beta cell mass which was calculated from relative volume of beta-cells and weight of each portions was 1.3+/-0.3 g, ranging from 1.2 g to 1.9 g (head 0.6+/-0.3 g, body 0.4+/-0.2 g, tail 0.4+/-0.2 g). Mean insulin content per pancreas was 63.6+/-46.6 g, ranging from 27.8 to 137.2 g/pancreas (head 25.1+/- 19.1 g, body 20.8+/-15.5 g, tail 17.7+/-14.9 g). In diabetic patients, relative volume of beta cells in tissues were variable from 0.4% to 2.8% and there was good correlation between beta-cell mass and body mass index of the diabetic patients. However we can't find the correlation among relative volume of beta-cell, (r2=0.55, p<0.05) duration of diabetes and age. Remarkable heterogeneity for loss of beta-cells in the islets of diabetic patients was observed even in the same lobe of pancreas. There were no evidence of lymphocytic infiltration in the islets. CONCLUSION: Insufficient beta cell mass seems to be a main cause for insulin secretory impairment in non-obese type 2 diabetic patients in Korea.

Diabetes Metab J : Diabetes & Metabolism Journal
Close layer
TOP