語系:
繁體中文
English
說明(常見問題)
登入
回首頁
切換:
標籤
|
MARC模式
|
ISBD
PKA activity in the pancreatic beta-...
~
ProQuest Information and Learning Co.
PKA activity in the pancreatic beta--cell enhances insulin secretion and improves glycemic control.
紀錄類型:
書目-語言資料,手稿 : Monograph/item
正題名/作者:
PKA activity in the pancreatic beta--cell enhances insulin secretion and improves glycemic control./
作者:
Kaihara, Kelly Asako.
面頁冊數:
1 online resource (152 pages)
附註:
Source: Dissertation Abstracts International, Volume: 73-11(E), Section: B.
Contained By:
Dissertation Abstracts International73-11B(E).
標題:
Cellular biology. -
電子資源:
click for full text (PQDT)
ISBN:
9781267472540
PKA activity in the pancreatic beta--cell enhances insulin secretion and improves glycemic control.
Kaihara, Kelly Asako.
PKA activity in the pancreatic beta--cell enhances insulin secretion and improves glycemic control.
- 1 online resource (152 pages)
Source: Dissertation Abstracts International, Volume: 73-11(E), Section: B.
Thesis (Ph.D.)--The University of Chicago, 2012.
Includes bibliographical references
This project centers on a novel mouse model of pancreatic beta-cell protein kinase A (PKA) signaling. Activation of PKA in the beta-cell results in enhanced insulin secretion. At the time that this mouse model was generated in 2006, a new class of pharmacological agents had recently been approved for the treatment of Type 2 Diabetes Mellitus (T2DM). These drugs activated beta-cell PKA activity through glucagon-like peptide-1 (GLP-1) signaling to improve insulin secretion and impact positively on glycemic control. However, how much of the improvement in glycemic control was attributed to a beta-cell phenotype was confounded by the many off target effects of GLP-1 upon other tissues. Moreover, GLP-1 activates two downstream targets in the beta-cell through increases in 3',5'-cyclic monophosphate (cAMP) levels: PKA and cAMP-regulated guanine nucleotide exchange factor (cAMP-GEF) known as EPAC. Both have been implicated in the potentiation of insulin secretion however their relative contributions are contested within the field. At this point in time there existed no mouse model of altered beta-cell PKA activity. The overall goal of this project was to determine the sole effects of increased beta-cell PKA activity on insulin secretion at a physiological level. To accomplish this, a mouse model of beta-cell specific constitutively active PKA signaling was generated hereafter referred to as beta-C&agr;R mice. Results demonstrate that PKA activity enhanced both the acute and sustained phases of insulin secretion under hyperglycemic conditions, but after a single glucose challenge, only enhancement at the acute phase was observed. Moreover, beta-cell PKA activity changed the dynamics of insulin release that promoted a 'first burst' of insulin within 2 minutes of a glucose challenge that was not observed in control animals. It is well established that individuals that progress to T2DM show a reduction at the acute phase of insulin release. The novel phenotype in the beta-C&agr;R mice allowed for physiological studies that addressed the consequences of solely increasing the acute phase for regaining glucose control. The data show that increased insulin secretion at the acute phase not only improved glucose homeostasis throughout aging, but also reversed pre-established glucose intolerance, representing a novel strategy for the treatment of T2DM.
Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2018
Mode of access: World Wide Web
ISBN: 9781267472540Subjects--Topical Terms:
1148666
Cellular biology.
Index Terms--Genre/Form:
554714
Electronic books.
PKA activity in the pancreatic beta--cell enhances insulin secretion and improves glycemic control.
LDR
:03632ntm a2200337Ki 4500
001
917939
005
20181022132250.5
006
m o u
007
cr mn||||a|a||
008
190606s2012 xx obm 000 0 eng d
020
$a
9781267472540
035
$a
(MiAaPQ)AAI3517160
035
$a
(MiAaPQ)uchicago:11402
035
$a
AAI3517160
040
$a
MiAaPQ
$b
eng
$c
MiAaPQ
$d
NTU
100
1
$a
Kaihara, Kelly Asako.
$3
1192138
245
1 0
$a
PKA activity in the pancreatic beta--cell enhances insulin secretion and improves glycemic control.
264
0
$c
2012
300
$a
1 online resource (152 pages)
336
$a
text
$b
txt
$2
rdacontent
337
$a
computer
$b
c
$2
rdamedia
338
$a
online resource
$b
cr
$2
rdacarrier
500
$a
Source: Dissertation Abstracts International, Volume: 73-11(E), Section: B.
500
$a
Adviser: Barton Wicksteed.
502
$a
Thesis (Ph.D.)--The University of Chicago, 2012.
504
$a
Includes bibliographical references
520
$a
This project centers on a novel mouse model of pancreatic beta-cell protein kinase A (PKA) signaling. Activation of PKA in the beta-cell results in enhanced insulin secretion. At the time that this mouse model was generated in 2006, a new class of pharmacological agents had recently been approved for the treatment of Type 2 Diabetes Mellitus (T2DM). These drugs activated beta-cell PKA activity through glucagon-like peptide-1 (GLP-1) signaling to improve insulin secretion and impact positively on glycemic control. However, how much of the improvement in glycemic control was attributed to a beta-cell phenotype was confounded by the many off target effects of GLP-1 upon other tissues. Moreover, GLP-1 activates two downstream targets in the beta-cell through increases in 3',5'-cyclic monophosphate (cAMP) levels: PKA and cAMP-regulated guanine nucleotide exchange factor (cAMP-GEF) known as EPAC. Both have been implicated in the potentiation of insulin secretion however their relative contributions are contested within the field. At this point in time there existed no mouse model of altered beta-cell PKA activity. The overall goal of this project was to determine the sole effects of increased beta-cell PKA activity on insulin secretion at a physiological level. To accomplish this, a mouse model of beta-cell specific constitutively active PKA signaling was generated hereafter referred to as beta-C&agr;R mice. Results demonstrate that PKA activity enhanced both the acute and sustained phases of insulin secretion under hyperglycemic conditions, but after a single glucose challenge, only enhancement at the acute phase was observed. Moreover, beta-cell PKA activity changed the dynamics of insulin release that promoted a 'first burst' of insulin within 2 minutes of a glucose challenge that was not observed in control animals. It is well established that individuals that progress to T2DM show a reduction at the acute phase of insulin release. The novel phenotype in the beta-C&agr;R mice allowed for physiological studies that addressed the consequences of solely increasing the acute phase for regaining glucose control. The data show that increased insulin secretion at the acute phase not only improved glucose homeostasis throughout aging, but also reversed pre-established glucose intolerance, representing a novel strategy for the treatment of T2DM.
533
$a
Electronic reproduction.
$b
Ann Arbor, Mich. :
$c
ProQuest,
$d
2018
538
$a
Mode of access: World Wide Web
650
4
$a
Cellular biology.
$3
1148666
650
4
$a
Nutrition.
$3
581367
655
7
$a
Electronic books.
$2
local
$3
554714
690
$a
0379
690
$a
0570
710
2
$a
ProQuest Information and Learning Co.
$3
1178819
710
2
$a
The University of Chicago.
$b
Molecular Metabolism and Nutrition.
$3
1192139
773
0
$t
Dissertation Abstracts International
$g
73-11B(E).
856
4 0
$u
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3517160
$z
click for full text (PQDT)
筆 0 讀者評論
多媒體
評論
新增評論
分享你的心得
Export
取書館別
處理中
...
變更密碼[密碼必須為2種組合(英文和數字)及長度為10碼以上]
登入