2型糖尿病中国地鼠脂肪肝相关胰岛素抵抗的形成机制

doi:10.11569/wcjd.v19.i5.457

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世界华人消化杂志

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基础研究

世界华人消化杂志. 2011-02-18; 19(5): 457-466
在线出版 2011-02-18. doi: 10.11569/wcjd.v19.i5.457

表1 实时荧光定量PCR引物列表

引物名称	序列号	引物序列
SREBP-1a	NM_011480	5'-ATGGACGAGCTGGCCTTCGGTGAGGCGGC-3'
		5'-CAGGAAGGCTTCCAGAGAGGA-3'
SREBP-1c	NM_011480	5'-GCTGTTGGCATCCTGCTATC-3'
		5'-TAGCTGGAAGTGACGGTGGT-3'
SREBP-2	U12330	5'-AGCTGGCAAATCAGAAAAACAAG-3'
		5'-GATTAAAGTCTTCAATCTTCAAGTCCAC-3'
LXRα	AJ132601	5'-TCAGCATCTTCTCTGCAGACCGG-3'
		5'-TCATTAGCATCCGTGGGAACA-3'
LXRβ	NM_009473	5'-AAGCAGGTGCCAGGGTTCT-3'
		5'-TGCATTCTGTCTCGTGGTTGT-3'
PPARα	NM_011144	5'-TGAGGAAGCCGTTCTGTGAC-3'
		5'-GGTGTCATCTGGATGGTTGC-3'
PPARβ/δ	NM_011145	5'-GCCTCGGGCTTCCACTAC-3'
		5'-AGATCCGATCGCACTTCTCA-3'
PPARγ	NM_011146	5'-CCCCTGCTCCAGGAGATCTAC-3'
		5'-GCAATCAATAGAAGGAACACGTTGT-3'
HMG-CoA reductase	X00494	5'-AGATACTGGAGAGTGCCGAGAAA-3'
		5'-TTTGTAGGCTGGGATGTGCTT-3'
HMG-CoA synthase	L00326	5'-CCTGGGTCACTTCCTTTGAATG-3'
		5'-GATCTCAAGGGCAACGATTCC-3'
LDLR	NM_010700	5'-CCAACCTGAAGAATGTGGTG-3'
		5'-CAGGTCCTCACTGATGATGG-3'
FAS	NM007988	5'-CACAGATGATGACAGGAGATGG-3'
		5'-TCGGAGTGAGGCTGGGTTGAT-3'
SCD-1	NM009127	5'-TGGGTTGGCTGCTTGTG-3'
		5'-GCGTGGGCAGGATGAAG-3'
ACC	AF356089	5'-ACACTGGCTGGCTGGACAG-3'
		5'-CACACAACTCCCAACATGGTG-3'
PEPCK	NM_011044	5'-GAGTTCCTGCCTCTCTCCAC-3'
		5'-TTCCACGAACTTCCTCACTG-3'
G-6-pase	U00445	5'-CATCAATCTCCTCTGGGTGGC-3'
		5'-TGTTGCTGTAGTAGTCGGTGTCC-3'
PGC-1α	BC066868	5'-TCTGGAACTGCAGGCCTAACTC-3'
		5'-GCAAGAGGGCTTCAGCTTTG-3'
CYP7A1	NM_007824	5'-AGCAACTAAACAACCTGCCAGTACTA-3'
		5'-GTCCGGATATTCAAGGATGCA-3'
Gck	NM_010292	5'-AGAGCAGATCCTGGCAGAGT-3'
		5'-TGGTTCCTCCCAGGTCTAAG-3'
Acox	NM_053115	5'-CCAGGACAGAGGTTCTTGGT-3'
		5'-TCTCAGGAAGGACTTGGCTT-3'
Cpt1	NM_013495	5'-CTCAGTGGGAGCGACTCTTCA-3'
		5'-GGCCTCTGTGGTACACGACAA-3'
Acadm	NM_007382	5'-TGACGGAGCAGCCAATGA-3'
		5'-ATGGCCGCCACATCAGA-3'
LPL	NM_008509	5'-GCCCAGCAACATTATCCAGT-3'
		5'-GGTCAGACTTCCTGCTACGC-3'
FAT / CD36	NM_007643	5'-GCCAAGCTATTGCGACATGA-3'
		5'-GATAGACCTGCAAATGTCAGAGGAA-3'
aP2	NM_024406	5'-AACACCGAGATTTCCTT-3'
		5'-ACACATTCCACCACCAG-3'
β-actin	AY618569	5'-AGAGGGAAATCGTGCGTGAC-3'
		5'-CAATAGTGATGACCTGGCCGT-3'

表2 正常对照组、胰岛素抵抗组和2型糖尿病组地鼠的代谢表型特征 (mean±SD, n = 10)

	正常对照组	胰岛素抵抗组	2型糖尿病组
体质量(g)	123.6±9.9	144.3±8.7^a	143.4±8.3^a
肝质量(g)	3.57±0.66	5.55±0.95^a	6.10±0.62^a
肝质量/体质量(%)	2.7±0.3	3.7±0.4^a	4.1±0.1^a^c
血糖(mmol/L)	4.33±0.61	6.56±0.90^a	11.00±1.22^a^c
血胰岛素(μg/L)	0.91±0.14	1.95±0.28^a	1.52±0.25^a^c
TG(mmol/L)	1.91±0.33	7.38±0.81^a	7.83±0.75^a
FFAs(mmol/L)	1.23±0.31	6.27±0.96^a	6.41±0.89^a
LDL(mmol/L)	1.89±0.25	10.20±0.82^a	11.95±1.58^a^c
HDL(mmol/L)	1.60±0.14	1.18±0.28^a	1.13±0.21^a
TC(mmol/L)	6.22±0.65	14.66±1.97^a	15.76±1.82^a
G₀×I₀	105.02±14.62	240.80±58.07^a	310.60±70.00^a^c
IR_HOMA	4.48±0.54	10.70±2.58^a	14.40±3.10^a^c
QUICKI	0.3061±0.007	0.2752±0.007^a	0.2621±0.006^a

QUICKI = 1/(logI₀+logG₀), 其中I₀为空腹胰岛素, 其单位是mU/L, G₀为空腹血糖, 其单位是mg/dL; HOMA-IR或IR_HOMA = 空腹血糖(mmol/L)×空腹胰岛素(mU/L)/22.5; G₀×I₀(G₀为空腹血糖, 其单位是mmol/L, I₀为空腹胰岛素, 其单位是mU/L).

^aP<0.05 vs 对照组,

^cP<0.05 vs 2型糖尿病组.

表3 胰岛素抵抗地鼠和2型糖尿病地鼠肝脏中基因表达芯片显示的部分与糖脂代谢相关的差异表达基因

序列号	基因名称	胰岛素抵抗组(倍数变化)	2型糖尿病组(倍数变化)	调解者¹
NM_007988	fatty acid synthase (Fasn)	2.26	3.99	SREBP-1
BE865030	acetyl-Coenzyme A carboxylase (ACC)	2.04	3.33	SREBP-1
NM_009127	Stearoyl CoA desaturase 1(Scd1)	2.57	4.27	SREBP-1
NM_053115	acyl-Coenzyme A oxidase	-1.99	-2.66	PPARα
NM_013495	carnitine palmitoyltransferase 1, liver (Cpt1)	-1.90	-2.60	PPARα
NM_007382	acetyl-Coenzyme A dehydrogenase, medium chain (Acadm)	-2.09	-2.75	PPARα
NM_007824	cytochrome P450, family 7, subfamily a, polypeptide 1 (Cyp7a1)	-2.00	-3.02	LXRα
BM937289	3-hydroxy-3-methylglutaryl-coenzyme A reductase(Hmgcr)	2.03	3.02	SREBP-2
NM_145942	3-hydroxy-3-methylglutaryl-Coenzyme A synthase (Hmgcs)	1.72	3.83	SREBP-2
NM_010700	low density lipoprotein receptor (Ldlr)	1.97	2.87	SREBP-2
NM_007643	CD36 antigen (Cd36) CD36/ FAT	2.02	3.31	PPARγ
NM_010292	glucokinase (Gck)	-2.05	-2.99	LXRα
NM_008061	glucose-6-phosphatase, catalytic (G6pc)	1.89	2.37	LXRα
NM_011044	phosphoenolpyruvate carboxykinase 1, cytosolic (Pck1)	1.90	3.61	LXRα
NM_011480	sterol regulatory element binding factor 1 (Srebf1)	2.76	3.72	LXRα
XM_127995	sterol regulatory element binding factor 2 (Srebf2)	2.65	3.38
NM_013839	nuclear receptor subfamily 1, group H, member 3 (Nr1h3)	-2.07	-2.80	LXRα
NM_009473	nuclear receptor subfamily 1, group H, member 2 (Nr1h2)	NC	NC
NM_011144	peroxisome proliferator activated receptor alpha (Ppara)	-2.13	-3.14
NM_011145	peroxisome proliferator activator receptor delta (Ppard)	-2.03	-2.82
NM_011146	peroxisome proliferator activated receptor gamma (Pparg)	2.18	2.91
NM_008509	lipoprotein lipase (Lpl)	2.06	3.79	PPARγ
NM_024406	fatty acid binding protein 4, adipocyte (Fabp4), aP2	2.17	3.87	PPARγ
NM_008904	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha (Ppargc1a)	2.20	3.21	LXRα

¹在后续研究中确定基因的主要调解者. NC表示无变化.

引文著录: 李国生, 刘栩晗, 黄澜, 朱华, 刘亚莉, 马春梅. 2型糖尿病中国地鼠脂肪肝相关胰岛素抵抗的形成机制. 世界华人消化杂志 2011; 19(5): 457-466