Online Submissions:http://www.journaltcm.

com J Tradit Chin Med 2012 September 15; 32(3): 446-452

[email protected] ISSN 0255-2922
© 2012 JTCM. All rights reserved.

BASIC INVESTIGATION

Antihyperglycemic and antihyperlipidemic action of cinnamalde-

hyde in C57blks/j Db/db mice

Juane Li, Tonghua Liu, Lei Wang, Xiangyu Guo, Tunhai Xu, Lili Wu, Lingling Qin, Wen Sun
aa
Juane Li, Shaanxi Provincial People's Hospital, Xi'an, RESULTS: 1) CA decreased serum levels of FBG and
Shaanxi 710068, China insulin as well as body weight in db/db mice; 2) CA
Tonghua Liu, Lei Wang, Xiangyu Guo, Tunhai Xu, Lili Wu, increased serum HDL-C levels; 3) CA significantly
Lingling Qin, Wen Sun, Beijing University of Chinese Medi-
decreased the mRNA expression of TNF-α in adi-
cine, Beijing 100029, China
Supported by International Science and Technology Coop-
pose tissue and upregulated mRNA expression of
eration Project (grant number 2009DFA31520), Innovation GLUT-4 in skeletal muscle; 4) protein expression of
Team Project of Beijing University of Chinese Medicine p-Akt was increased in CA-treated mice, but Akt,
(2011-CXTD-19) and Beijing Municipal Education Commis- AMPKα and p-AMPKα showed no change.
sion (2011)
Correspondence to: Prof. Tonghua Liu, Science and Tech- CONCLUSION: CA has antihyperglycemic and anti-
nology Department, Beijing University of Chinese Medicine, hyperlipidemic actions in db/db mice and could be
Beijing 100029, China. [email protected] useful in the treatment of type-2 diabetes.
Telephone: +86-10-64286642
Accepted: May 05, 2012
© 2012 JTCM. All rights reserved.

Key words: Cinnamaldehyde; Diabetes mellitus,

Abstract Type 2; Insulin resistance

OBJECTIVE: To investigate the effects of cinnamal-

dehyde (CA), an active and major compound in cin- INTRODUCTION
namon, on glucose metabolism and insulin resis-
tance in C57BLKS/J db/db mice. Type-2 diabetes mellitus (T2DM) is a chronic metabol-
ic disorder known to have affected »4% of adults aged ≥
METHODS: Sixteen male C57BLKS db/db mice 20 years in 1995, and is expected to affect 380 million
were randomly divided into control and CA treat- by 2025.1 The cause of T2DM is not known, although
ment groups. CA was given (20 mg·kg – 1·day – 1, p. genetic and environmental factors (e.g. obesity, lack of
o.) for 4 weeks. Pure water was given to control and exercise) appear to play a part. T2DM occurs if the
db/+ mice. Subsequently, the levels of fasting pancreas does not produce sufficient amounts of insu-
blood glucose (FBG), fasting serum insulin, triglyer- lin or if the body cannot effectively use the insulin it
ide, cholesterol, low-density lipoprotein -cholester- produces.2 Insulin resistance is a major contributor to
ol (LDL-C), high-density lipoprotein-cholesterol the pathogenesis of T2DM and has a key role in associ-
(HDL-C), and free fatty acids (FFA), as well as the ated metabolic abnormalities such as hyperlipidemia
mRNA content of adiponectin and tumor necrosis and hypertension.3
factor (TNF)-α in adipose tissue, glucose transport- Several types of anti-diabetic medicines have been stud-
er type 4 (GLUT-4) in skeletal muscle, and protein ied for their ability to lower blood glucose and ulti-
expressions of Akt, phospho-Akt (Thr308), AMPKα, mately lower the prevalence of secondary complica-
phospho-AMPKα (Thr172) in skeletal muscle were tions of this disease. There is growing interest in folk
measured. remedies using herbs due to the side effects associated

JTCM | www. journaltcm. com 446 September 15, 2012 | volume 32 | Issue 3 |
 Li JE et al. Action of cinnamaldehyde in C57blks/j Db/db mice

with the synthetic medicines used in the treatment of group and control group were given an equivalent vol-
T2DM. Cinnamon is the bark of Cinnamomi cassise ume of pure water alone (0.5% DMSO) by intragastric
(Lauraceae). It is a traditional folk medicine used in administration once a day for 4 weeks. The CA dosage
China, Korea and Russia for the treatment of T2DM.4 was chosen based on that used in three reports.10,14,17
Interest in this herb has increased since the discovery of
its potential effects on insulin5 and its ability to reduce Measurement of FBG, serum insulin, HOMA-IR,
levels of fasting blood glucose (FBG) and plasma lipids blood lipids and body weight
in humans.6 Subsequently, some studies have reported FBG was measured immediately with a Glucometer
that cinnamon extract decreases blood glucose,7 im- (ACC U-Check; Roche, Basel, Switzerland) in tail-vein
proves glucose uptake in adipocytes,8 and improves the blood (≈5 μL each time) after fasting for 8 h on days
function of pancreatic islets9 in Wistar rats, as well as 7, 14, 21 and 28. After treatment for 4 weeks, mice
slowing down absorption of carbohydrates in the small were fasted overnight and anesthetized with pentobar-
intestine.10 Cinnamon extract significantly increases in- bital sodium (50 mg/kg, i.p.). Blood was collected
sulin sensitivity possibly by regulating the peroxisome from the abdominal aorta. Serum levels of insulin were
proliferator-activated receptor (PPAR)-medicated me- assayed with an enzyme-linked immunoassay (ELISA)
tabolism of glucose and lipids11 as well as increasing the kit (Linco Research, St Charles, MO, USA). Indices of
amount of proteins involved in insulin signaling, glu- insulin resistance were calculated using the homeostasis
cose transport, and anti-inflammatory/anti-angiogene- model of insulin resistance (HOMA-IR) index21 where-
sis responses.11,12 by:
The active compounds of cinnamon have been report- HOMA-IR=fasting blood glucose level (mmol/L) × se-
ed. These include water-soluble polyphenol type-A rum insulin level (ng/mL)/22.5
polymers,8,11,13 cinnamaldehyde (CA)14-17 and procyani- Serum levels of triglyceride (TG), total cholesterol
din oligomers.18 As a major and effective compound (TC), low-density lipoprotein-cholesterol (LDL-C),
isolated from cinnamon,19,20 CA possesses anti-hypogly- high-density lipoprotein-cholesterol (HDL-C) and free
cemic and anti-hypolipidemic effects in streptozotocin fatty acids (FFAs) were measured using commercial
(STZ)-induced T2DM in rats14,17 and improves the kits (Beijing North Institute of Biological Technology,
function of pancreatic islets.9 However, reports on the Beijing, China) with an Automatic Biochemical Ana-
effect of CA on the metabolism of glucose and lipids in lyzer (AU400 Biochemistry Analyzer, Olympus, Tokyo,
T2DM are lacking. The aim of the present study was Japan). Body weight was measured on days 7, 14, 21
to investigate the effect of CA in db/db mice, which and 28.
are used as models of obesity, insulin resistance and
T2DM. Preparation of total RNA
Frozen samples of quadriceps muscle and epididymal
METHODS fat tissues were crushed in liquid nitrogen. Total RNA
was extracted using Trizol reagent (Invitrogen, Carls-
Ethical approval of the study protocol bad, CA, USA). The relative purity of RNA was as-
The experimental protocols were approved by the Ani- sessed by spectrophotometric means. The ratio of ab-
mal Care and Use Committee of Beijing University of sorbance at 260 nm to that at 280 nm was 1.7-2.0 for
Chinese Medicine (Beijing, China). all preparations. The integrity of RNA was confirmed
in 1% agarose gel.
Animals
Sixteen 7-week-old male BKS. Cg-+ Leprdb/+ Leprdb/ mRNA analyses:
Jcl (db/db) mice and 8 non-diabetic littermate control Total RNA was reverse-transcribed by a Reverse Trans-
mice (db/+ ) were supplied by the Model Animal Re- fer kit (Beijing North Institute of Biological Technolo-
source Center of Nanjing University (Nanjing, China). gy) with oligo dT primers following the manufacturer's
The animals were kept in the air-conditioned Animal instructions. The sequences of sense and antisense
House of the Beijing University of Chinese Medicine primers used for amplification are shown in Table 1.
at 25° C-30° C and 45%-55% relative humidity. They GAPDH, glyceraldehyde 3-phosphate dehydrogenase;
were fed standard food (Beijing Ke Ao Xie Li, Beijing, TNF-α, tumor necrosis factor-α, GLUT4, glucose
China) ad libitum under a 12 h light-dark cycle transporter type 4.
throughout the study. Amplification was undertaken with an initial denatur-
ation at 95°C for 5 min followed by 30 cycles at 95°C
Oral administration (30 s), 55°C (30 s), and then extension at 72°C (30 s).
After being fed for 1 week, 16 db/db mice were divid- The polymerase chain reaction (PCR) products were
ed into two equal groups: CA and control. Mice in the separated on 1.0% agarose gel and stained with ethid-
CA group received CA solution (0.5% dimethyl sulfox- ium bromide. Glucose transporter type 4 (GLUT4)
ide (DMSO), 20 mg·kg – 1·day – 1; Shanghai Winherb mRNA was measured by denaturation at 95°C for 2 min
Medical Science, Shanghai, China). Mice in the db/+ followed by 45 cycles of PCR (95°C for 20 s, 58°C for

JTCM | www. journaltcm. com 447 September 15, 2012 | volume 32 | Issue 3 |
Li JE et al. Action of cinnamaldehyde in C57blks/j Db/db mice

25 s and 72°C for 30 s). Relative RNA levels were de- profiles were produced at the end of each reaction.
termined by analyzing the changes in SYBR green fluo- mRNA levels of all genes were normalized using glycer-
rescence during PCR using the ΔΔCt method. To con- aldehyde 3-phosphate dehydrogenase (GAPDH) as the
firm amplification of specific transcripts, melting-curve internal control.
Table 1 Sequences of sense and antisense primers used for amplification

Sense Anti-sense

GAPDH (122 bp) TGG AGA AAC CTG CCA AGT GTT GCT GTT GAA GTC GCA

TNF-α (204 bp) CGT AGC AAA CCA CCA AGT G ATA GCA AAT CGG CTG ACG

Adiponectin (149 bp) CAT TAT GAC GGC AGC ACT G TCC TGA TAC TGG TCG TAG GTG
GAG CCC CAG ATA CCT CTA CAT AGC TAG TGC GTC AGA CAC ATC
GLUT4 (100 bp)
CAT AGA

Western blotting and CA group (both P<0.01) (Figure 3). Serum con-
The extracted protein samples of muscle tissues were centrations of HDL-C in the CA group increased sig-
separated on sodium dodecyl sulfate (SDS) polyacryl- nificantly as compared with the control group. Howev-
amide gels and electrotransferred onto polyvinylidene er, no statistically significant differences in the levels of
difluoride (PVDF) membranes. PVDF membranes FFAs, TG, TC and LDL-C between the two groups
were incubated with primary antibody (anti-Akt, an- was noted (P=0.16, 0.58, 0.07 and 0.40, respectively).
ti-phospho-Akt (Thr 308), anti-AMPKα and antiphos-
pho- AMPKα (Thr 172; Cell Signaling Technology,
Serum levels of insulin and the HOMA-IR index
Danvers, MA, USA). Detection of immunoreactive
Serum levels of insulin and the HOMA-IR index in
bands was done using an Electrochemiluminescence
the CA group and control group were significantly
kit (Beijing North Institute of Biological Technology).
higher than those in the db/+ group (Figure 4), and sig-
Densitometry was undertaken by scanning the radio-
nificant differences were observed between the CA
graphs using the Image J 1.4.3 system (Media Cyber-
group and control group.
netics, Bethesda, MD, USA).

Statistical analyses Changes in the mRNA expression of adiponectin and

Statistical analyses were undertaken using SPSS tumor necrosis factor (TNF)-α in adipose tissue
ver13.0 (SPSS, Chicago, IL, USA). Data are the mean± Expression of adiponectin and TNF-α in white adi-
standard deviation. Comparisons among the groups pose tissue is shown in Figure 5. TNF-α mRNA levels
were analyzed by one-way analysis of variance (ANO- in the CA group were significantly decreased as com-
VA) followed by Dunnett's test. P<0.05 was consid- pared with those in the control group. However, there
ered significant. was no significant difference in adiponectin mRNA ex-
pression between the CA group and control group.
RESULTS
Changes in protein levels of Akt, p-Akt, AMPKα and
Body weight p-AMPKα as well as mRNA expression of GLUT4 in
The changes in body weight after CA administration muscle tissue
for 4 weeks are shown in Figure 1 Body weight in the p-Akt protein expression and GLUT4 mRNA expres-
db/+ group was significantly lower than that in the con- sion increased significantly in the CA group as com-
trol and CA group during the 4-week treatment. Body pared with the control group (both P<0.05) (Figure 6).
weight in the control group was higher than that in the However, protein expression of Akt, p-AMPKα and
CA group on day 28 (P<0.05). AMPKα did not significantly change in the CA group
as compared with the control group.
FBG levels
During the entire experiment, FBG levels in the con-
trol group and CA group were significantly higher that DISCUSSION
those in the db/+ group (Figure 2). On day 28, FBG
levels in the CA group showed a significant reduction When genetic obesity is produced by complete knock-
compared with the control group. out of the leptin receptor via the db mutation, db/db
mice develop severe resistance to insulin, resulting in se-
Serm levels of TG, TC, HDL-C, LDL-C and FFAs vere hyperglycemia and, ultimately, premature death
There were significant differences in all of the lipid lev- due to insufficient insulin action. 23 In the KS genetic
els in the db/+ group compared with the control group background, hyperglycemia secondary to severe obesi-

JTCM | www. journaltcm. com 448 September 15, 2012 | volume 32 | Issue 3 |
 Li JE et al. Action of cinnamaldehyde in C57blks/j Db/db mice

a a a
a
a b

Figure 1 Effects of CA on body weight during 4-week treatment

CA group and control group compared with the db/+ group, aP<0.001; on day 28, the CA group compared with the control group,
b
P<0.05.

a a a
a a
b

Figure 2 Effects of CA on fasting blood glucose levels during 4-week treatment

Control group and CA group compared with the db/+ group, aP<0.001; on day 28, the CA group compared with the control
group, bP<0.05.
b 梵蒂冈的和
b

b
b b a
b c

b
b

Figure 3 Serum levels of lipids and FFAs in the treatment groups

Compared with the db/+ group bP<0.01; compared with the control group, cP<0.05.
c
c
b
b
a b

Figure 4 Effects of CA on serum levels of insulin and the HOMA-IR index

a
P<0.05, bP<0.01 vs. the db/+ group; cP<0.05 vs. the control group.

JTCM | www. journaltcm. com 449 September 15, 2012 | volume 32 | Issue 3 |
Li JE et al. Action of cinnamaldehyde in C57blks/j Db/db mice

TNF-α/GAPDH
a
a a
a

Figure 5 Effects of CA on mRNA expressions of adiponectin and TNF-α in adipose tissue

a
P<0.01 vs. the db/+ group; bP<0.05 vs. the control group.
c
Akt&p-Akt/β-actin

AMPKα&p-AMPKα/
a b
a

β-actin
b

AMPKα p-AMPKα

b
b

Figure 6 Effects of CA on protein expressions of Akt, p-Akt, AMPKα and p-AMPKα and mRNA of GLUT4 in skeletal muscle tissue
a
P<0.05, bP<0.01 vs the db/+ group; cP<0.05 vs the control group.
ty-induced insulin resistance worsens with increase in pression in the quadriceps muscle.28,29 Although we did
age.23 This particular inbred strain is an ideal model to not observe insulin-stimulated Akt kinase activity or
investigate the effect of CA on glucose metabolism and GLUT4 translocation, increases in the mRNA expres-
insulin resistance in T2DM. sion of GLUT4 and protein expression of p-Akt(Thr
The results of the present study clearly showed that CA 308) in skeletal muscle suggested that the anti-diabetic
produced a mild hypoglycemic effect after 4-week treat- effects of CA could be achieved by influencing the
ment in mice. More importantly, CA treatment signifi- stimulation and translocation of GLUT4 in insulin-re-
cantly decreased the body weight, serum insulin level sistant skeletal muscle. These results may be consistent
and HOMA-IR index along with improvement in se- with those of Anand et al., which showed that CA re-
rum levels of HDL-C. The anti-diabetic effect of CA sults in the translocation of membrane GLUT4 in skel-
in db/db mice may be due to an improvement in insu- etal muscle after 60-day treatment in STZ-induced
lin sensitivity and loss of body weight. These results T2DM in rats.17
suggest that CA has mild hypoglycemic and hypolipid- The adenosine monophosphate-activated protein ki-
emic effects in obesity and insulin resistance, in con- nase (AMPK) pathway plays an important part in regu-
trast to findings from previous reports.14 lation of the metabolism of lipids and glucose. In addi-
Insulin resistance is a major factor in the pathogenesis tion, AMPK promotes glucose uptake into skeletal
of T2DM. It is induced primarily by decreases in the muscle and suppresses glucose output from the liver
insulin stimulation of glucose transport and metabo- via insulin-independent mechanisms.30 In our previous
lism in muscles and adipocytes.24,25 Insulin-stimulated study, western blotting analyses showed that the level
glucose transport is known to occur through transloca- of phosphorylated AMPK (Tyr172)31 in the skeletal
tion of GLUT4 from the intracellular pool to the plas- muscle of db/db mice was significantly lower than that
ma membrane. Signaling downstream of PI3-kinase in db/+ mice, and was not significantly enhanced by
(PI3K) to GLUT4 translocation appears to be mediat- CA treatment. It has been suggested that CA may not
ed (at least in part) by serine/threonine protein kinase B increase AMPK activity in insulin-resistant muscles.
(PKB/Akt)26 which is activated by phosphorylation at Adipose tissue is increasingly recognized as an active en-
Thr308 residues.27 In db/db mice, glucose utilization docrine organ with many secretory products and to be
in skeletal muscle decreases significantly due to major part of the innate immune system. With obesity, mac-
defects in the activities of PI3K, PKB/Akt as well as rophages infiltrate adipose tissue, and numerous adipo-
atypical protein kinase C (aPKC) activation accompa- cytokines are released by macrophages and adipo-
nied by a significant reduction in GLUT-4 mRNA ex- cytes.32 Adipocytokines have important roles in the

JTCM | www. journaltcm. com 450 September 15, 2012 | volume 32 | Issue 3 |
 Li JE et al. Action of cinnamaldehyde in C57blks/j Db/db mice

pathogenesis of insulin resistance and associated meta- metic for insulin in 3T3-L1 adipocytes. J Am Coll Nutr
bolic complications such as dyslipidemia, hyperten- 2001; 20(4): 327-336.
sion, and premature heart disease. In addition to the 9 Ping H, Zhang G, et al. Antidiabetic effects of cinnamon
production of pro-inflammatory cytokines that pro- oil in diabetic KK-Ay mice. Food Chem Toxicol 2010; 48
mote metabolic complications, adipose tissue is the (8-9): 2344-2349.
sole source of adiponectin, which has anti-inflammato- 10 Kim SH, Hyun SH, Choung SY. Antioxidative effects of
ry actions and is associated with atherosclerosis.33,34 Cir- Cinnamomi cassiae and Rhodiola rosea extracts in liver of
culating levels of FFAs are increased in obesity and can diabetic mice. Biofactors 2006; 26(3): 209-219.
11 Cao H, Polansky MM, Anderson RA. Cinnamon extract
induce insulin resistance.35 The present study showed
and polyphenols affect the expression of tristetraprolin, in-
that CA decreased the expression of TNF-α in adipose
sulin receptor, and glucose transporter 4 in mouse 3T3-L1
tissue and serum levels of FFAs, which are possibly in-
adipocytes. Arch Biochem Biophys 2007; 459(2): 214-222.
duced by a loss in body weight, but CA acts as an "in-
12 Cao H, Graves DJ, Anderson RA. Cinnamon extract regu-
sulin sensitizer" according to our analysis on the tran-
lates glucose transporter and insulin-signaling gene expres-
scriptional level of PPARs (manuscript in preparation). sion in mouse adipocytes. Phytomedicine 2010; 17(13):
This was the first study to explore the effects and mech- 1027-1032.
anisms of CA on an obesity and insulin-resistance mod- 13 Anderson RA, Broadhurst CL, Polansky MM, et al. Isola-
el of T2DM. This is in contrast to a STZ-induced tion and characterization of polyphenol type-A polymers
model of T2DM, which is characterized by beta-cell from cinnamon with insulin-like biological activity. J Ag-
damage.36 In conclusion, CA exhibited hypoglycemic ric Food Chem 2004; 52(1): 65- 70.
and hypolipidemic effects in db/db mice along with 14 Subash Babu P, Prabuseenivasan S, Ignacimuthu S. Cin-
loss in body weight. This investigation revealed the po- namaldehyde a potential antidiabetic agent. Phytomedi-
tential use of CA or cinnamon as a natural alternative cine 2007; 14(1): 15-22.
treatment for T2DM and/or metabolic syndrome. 15 Chao LK, Chang WT, Shih YW, Huang JS. Cinnamalde-
hyde impairs high glucose-induced hypertrophy in renal
interstitial fibroblasts. Toxicol Appl Pharmacol 2010; 244
ACKNOWLEDGMENTS (2): 174-180.
16 Zhang W, Xu YC, Guo FJ, Meng Y, Li ML. Anti-diabetic
The authors thank Mr. Moriyama K. (Mukogawa effects of cinnamaldehyde and berberine and their impacts
Women's University, Nishinomiya, Japan) for his cri- on retinol-binding protein 4 expression in rats with type 2
tique of the manuscript. We are also grateful to Sun diabetes mellitus. Chin Med J (Engl) 2008; 121(21):
Biomedical Technology for technical assistance. 2124-2128.
17 Anand P, Murali KY, Tandon V, Murthy PS, Chandra R.
Insulinotropic effect of cinnamaldehyde on transcriptional
regulation of pyruvate kinase, phosphoenolpyruvate car-
REFERENCES boxykinase, and GLUT4 translocation in experimental dia-
1 International Diabetes Federation. Diabetes atlas, third betic rats. Chem Biol Interact 2010; 186(1): 72-81.
edition, 2006. www.eatlas.idf.org. 18 Lu Z, Jia Q, Wang R, et al. Hypoglycemic activities of A-
2 World Health Organization. Diabetes. 2009. Nov. www. and B-type procyanidin oligomer-rich extracts from differ-
who.int. ent Cinnamon barks. Phytomedicine 2010; online 20 Sep-
3 Goldstein BJ. Insulin resistance as the core defect in type tember 2010.
2 diabetes mellitus. Am J Cardiol 2002; 90(5A): 3G-10G. 19 Chang ST, Chen PF, Chang SC. Antibacterial activity of
4 Bailey CJ, Day C. Traditional plant medicines as treat- leaf essential oils and their constituents from Cinnamo-
ments for diabetes. Diabetes Care 1989; 12(8): 553-564. mum osmophloeum. J Ethnopharmacol 2001; 77(1):
5 Khan A, Bryden NA, Polansky MM, Anderson RA. Insu- 123-127.
lin potentiating factor and chromium content of selected 20 Cheng SS, Liu JY, Tsai KH, Chen WJ, Chang ST. Chemi-
foods and spices. Biol Trace Elem Res 1990; 24(3): cal composition and mosquito larvicidal activity of essen-
183-188. tial oils from leaves of different Cinnamomum osmo-
6 Khan A, Safdar M, Ali Khan MM, Khattak KN, Ander- phloeum provenances. J Agric Food Chem 2004; 52 (14):
son RA. Cinnamon improves glucose and lipids of people 4395-4400.
with type 2 diabetes. Diabetes Care 2003; 26(12): 21 Haffner SM, Kennedy E, Gonzalez C, Stern MP, Miettin-
3215-3218. en H. A prospective analysis of the HOMA model. The
7 Qin B, Nagasaki M, Ren M, Bajotto G, Oshida Y, Sato Y. Mexico City Diabetes Study. Diabetes Care 1996; 19(10):
Cinnamon extract (traditional herb) potentiates in vivo in- 1138-1141.
sulin- regulated glucose utilization via enhancing insulin 22 Kodama H, Fujita M, Yamaguchi I. Development of hy-
signaling in rats. Diabetes Res Clin Pract 2003; 62(3): perglycemia and insulin resisitance in conscious genetically
139-148. diabetic (c57bl/ksj-db/db) mice. Diabebetologia 1994; 37:
8 Jarvill-Taylor KJ, Anderson RA, Graves DJ. A hy- 739-744.
droxychalcone derived from cinnamon functions as a mi- 23 Leiter EH. Carboxypeptidase E and obesity in the mouse.
J Endocrinol 1997; 155(2): 211-214.

JTCM | www. journaltcm. com 451 September 15, 2012 | volume 32 | Issue 3 |
Li JE et al. Action of cinnamaldehyde in C57blks/j Db/db mice

24 Kahn CR. Banting lecture: insulin action, diabetogenes, kinase. Acta Physiol (Oxf ) 2009; 196(1): 129-145.
and the cause of type II diabetes. Diabetes 1994; 43: 31 Zhang BB, Zhou G, Li C. AMPK: an emerging drug tar-
1066-1084. get for diabetes and the metabolic syndrome. Cell Metab
25 Rasouli N, Kern PA. Adipocytokines and the metabolic 2009; 9(5): 407-416.
complications of obesity. J Clin Endocrinol Metab 2008; 32 Rasouli N, Kern PA. Adipocytokines and the Metabolic
93 (11 Suppl 1): S64-S73. Complications of Obesity. J Clin Endocrinol Metab 2008;
26 Coffer PJ, Jin J, Woodgett JR. Protein kinase B (c-Akt): A 93(11 Suppl 1): S64-S73.
multifunctional mediator of phosphatidylinositol 3-kinase 33 Scherer PE, Williams S, Fogliano M, Baldini G, Lodish
activation. Biochem J 1998; 335: 1-13. HF. A novel serum protein similar to C1q, produced exclu-
27 Meyer MM, Levin K, Grimmsmann T, Beck-Nielsen H,
sively in adipocytes. J Biol Chem 1995; 270: 26746-
Klein HH. Insulin signaling in skeletal muscle of subjects
26749.
with or without Type II-diabetes and first degree relatives
34 Kumada M, Sumitsuji S. Association of hypoadiponec-
of patients with the disease. Diabetologia 2002; 45(6):
tinemia with coronary artery disease in men. Arterioscler
813-822.
Thromb Vasc Biol 2003; 23: 85-89.
28 Hori H, Sasaoka T, Ishihara H, et al. Association of
SH2-containing inositol phosphatase 2 with the insulin re- 35 Richard N. Bergman, Marilyn Ader. Free Fatty Acids and
sistance of db/db mice. Diabetes 2002; 51: 2387-2394. Pathogenesis of Type 2 Diabetes Mellitus. Trends in Endo-
29 Shao J, Yamashita H, Qiao L, Friedman JE. Decreased crinology and Metabolism 2000; 11(9): 351-356.
Akt kinase activity and insulin resistance in C57BL/ 36 Lukic ML, Stosic-Grujicic S, Shahin A. Effector mecha-
KsJ-Leprdb/db mice. J Endocrinol 2000; 167(1): 107-115. nisms in low-dose streptozotocin- induced diabetes. Dev
30 Hegarty BD, Turner N, Cooney GJ, Kraegen EW. Insulin Immunol 1998; 6(1-2): 119-128.
resistance and fuel homeostasis: the role of AMPK protein

JTCM | www. journaltcm. com 452 September 15, 2012 | volume 32 | Issue 3 |