성장기 흰쥐에서 단백질 결핍과 장기간 알코올 투여가 인슐린 분비능 및 감수성에 미치는 영향

Abstract

[한글]

인슐린 비의존형 당뇨병은 유전적 또는 환경적 요인에 의해 인슐린 분비능과 감수성의 저하로 발생한다고 알려져 있다. 본 연구에서는 환경인자 중에서 특히 성장기의 단백질결핍과 장기간 알코올투여의 복합효과가 인슐린 분비능과 감수성에 미치는 영향을 알아보고

자 하였다. 실험동물은 수컷 Srague-Dawley계 휜쥐를 사용하여 각군당 20마리씩 단백질결핍+알코올투여군(1군), 단백질결핍 대조군(2군), 정상식이+알코올투여군(3군) 및 정상식이 대조군(4군)으로나누어, 생후 4주부터 12주까지 단백질결핍(단백질 함량 5%) 또는 정상(단백질 함량 20%)식이를 공급하고,8주부터 12주까지 알코올(5g/㎏/d) 또는 생리식염수를 투여하였다. 생후 12주가 된 횐쥐에서 단백질결핍과 알코올이 인슐린 분비능과 감수성에 미치는 영향을 비교하여 다음과 같은 결과를 얻었다.

1. 단백질결핍군은 정상식이군에 비해 현저한 성장 장애를 보였고, 정상식이군에서 알코올을 투여한 쥐의 성장이 대조군에 비해 감소되었다. 체중을 보정한 췌장의 무게비는 각 군간에 차이를 보이지 않았으나, 부고환주위 지방량은 2군이 4군에 비해 감소되었다.

2. 복강내 당부하에 따른 내당능은 1군에서 2군에 비해 향상되었으며, 인슐린 분비반응은 2군이 4군에 비해 현저하게 감소되어 있었으나 1군은 4군과 차이를 보이지 않았다.

3. 정상혈당 클램프검사에서 측정한 말초조직의 포도당이용율은 2군에서 4군에 비해 감소되어 있었으나 1군은 4군과 차이를 보이지 않았다. 검사후 채취한 골격근의 당원합성효소 활성도는 4군간에 차이를 보이지 않았다.

4. 췌장의 무게당 인슐린 저장량은 각 군간에 차이가 없었다.

5. 단백질결핍군의 췌장 소도의 장축 길이와 소도 세포 및 핵의 크기가 감소되어 있었으나, 1군에서 2군에 비해 소도세포와 핵의 크기가 상대적으로 증가되어 있었다. 이상의 결과로 성장기 횐쥐에서 단백질결핍은 성장후 인슐린 분비능과 감수성을 저하시키며 장기

간 중등도의 알코올투여는 단백질결핍에 의한 인슐린 분비능과 감수성의 저하를 정상화시키지만 정상식이군에서는 알코올의 영향이 나타나지 않아, 알코올이 포도당대사에 미치는 영향은 영양상태에 따라 다르게 나타남을 알 수 있었다

The combined effects of protein malnutrition and chronic alcohol intake on insulin

secretion and sensitivity in growing rats

Bong Soo Cha

Department of Medicine The School, Yonsei University

(Directed by Professor Kap Bum Huh)

This investigation was performed to examine the combined effects of protein

malnutrition and chronic moderate amount of alcohol intake on insulin secretory

capacity and sensitivity in growing rats. Weanling 4-wk-old male Sprague-Dawley

rats were fed low protein (5%, LP) or control (20%, C) diet from 4 to 12weeks and

alcohol (5g/kg/d) or saline gavage from 8 to 12 weeks. All rats were divided into 4

groups according to different diet protocols; group I: LP with alcohol, group Ⅱ:

LP with saline, group Ⅲ: C with alcohol, group Ⅳ: C with saline. At the age of 12

weeks, we determined the insulin secretory capacity and sensitivity in the four

different diet groups. The results are summarized as follows:

1. Normal weight gain was nearly completely arrested in LP groups compared to

group Ⅳ. In C groups, chronic alcohol intake decreased body weight gain.

Pancreatic weights adjusted with body weight were not different among the 4 groups,

but epididymal fat weight adjusted with body weight was decreased in group Ⅱ

compared to group Ⅳ.

2. Intraperitoneal glucose tolerance was improved in group Ⅰ compared to group

Ⅱ. Insulin responses to glucose challenge were markedly decreased in group Ⅱ

compared to group Ⅳ, but not in group Ⅰ.

3. Glucose disposal rate during euglycemic clamp test was diminished in group Ⅱ

compared to group Ⅳ, but there were no differences between group Ⅰ and group Ⅳ.

Glycogen synthase activities of skeletal muscle after 2 hour hyperinsulinemic state

were not different among the 4 groups.

4. There were no differences of reserved insulin content of whole pancreas

adjusted with pancreas weight among the 4 groups.

5. In light microscopic findings of pancreatic islets, sizes of islets, islet

cells and nuclei were decreased in LP groups compared to group Ⅳ. But sizes of

islet cells and nuclei were increased in group Ⅰ compared in group Ⅱ.

According to these results, the impaired insulin and decreased insulin

sensitivity due to protein malnutrition were restored by chronic, moderate amount

of alcohol intake in malnourished state, but these effects were not apparent in

protein sufficient state. Therefore, the effects of chronic alcohol intake

onglucose metabolism may be different according to the nutritional status, and

further studies for the effects of alcohol intake in lean diabetic patients are

required to extrapolate these results in human.

[영문]

This investigation was performed to examine the combined effects of protein malnutrition and chronic moderate amount of alcohol intake on insulin secretory capacity and sensitivity in growing rats. Weanling 4-wk-old male Sprague-Dawley rats were fed low protein (5%, LP) or control (20%, C) diet from 4 to 12weeks and

alcohol (5g/kg/d) or saline gavage from 8 to 12 weeks. All rats were divided into 4 groups according to different diet protocols; group I: LP with alcohol, group Ⅱ: LP with saline, group Ⅲ: C with alcohol, group Ⅳ: C with saline. At the age of 12

weeks, we determined the insulin secretory capacity and sensitivity in the four different diet groups. The results are summarized as follows:

1. Normal weight gain was nearly completely arrested in LP groups compared to group Ⅳ. In C groups, chronic alcohol intake decreased body weight gain.

Pancreatic weights adjusted with body weight were not different among the 4 groups, but epididymal fat weight adjusted with body weight was decreased in group Ⅱ compared to group Ⅳ.

2. Intraperitoneal glucose tolerance was improved in group Ⅰ compared to group Ⅱ. Insulin responses to glucose challenge were markedly decreased in group Ⅱ compared to group Ⅳ, but not in group Ⅰ.

3. Glucose disposal rate during euglycemic clamp test was diminished in group Ⅱ compared to group Ⅳ, but there were no differences between group Ⅰ and group Ⅳ.

Glycogen synthase activities of skeletal muscle after 2 hour hyperinsulinemic state were not different among the 4 groups.

4. There were no differences of reserved insulin content of whole pancreas adjusted with pancreas weight among the 4 groups.

5. In light microscopic findings of pancreatic islets, sizes of islets, islet cells and nuclei were decreased in LP groups compared to group Ⅳ. But sizes of islet cells and nuclei were increased in group Ⅰ compared in group Ⅱ.

According to these results, the impaired insulin and decreased insulin sensitivity due to protein malnutrition were restored by chronic, moderate amount of alcohol intake in malnourished state, but these effects were not apparent in protein sufficient state. Therefore, the effects of chronic alcohol intake onglucose metabolism may be different according to the nutritional status, and further studies for the effects of alcohol intake in lean diabetic patients are required to extrapolate these results in human.