Abstract
We examined the mechanisms and efficacy of Codonopsis lanceolata water extract (CLW) for treating type 2 diabetic (T2DM) symptoms. Partial pancreatectomized (Px) rats, a non-obese T2DM model, were provided high fat diets containing cellulose (control), 0.3% (CLW-L) or 1% CLW (CLW-H) for eight weeks. The positive control group was provided with rosiglitazone (20 mg/kg bw/day). The control group had lower epididymal fat masses than the CLW and the positive control groups, possibly due to urinary glucose loss, although CPT-1 and SIRT-1 expression was higher in the CLW group. CLW-H significantly reduced serum glucose levels and urinary glucose loss compared to the untreated control. The improvement of glucose utilization was associated with a higher fat mass in the CLW-H and positive control groups. Glucose-stimulated insulin secretion was higher in the untreated control than other groups and CLW tightly regulated insulin secretion as much as the positive control, and it was much tighter than the untreated control. Glucose infusion rates were higher during the hyperinsulinemic euglycemic clamp in the CLW and positive controls than the untreated control, and liver glucose outputs were lower during basal and hyperinsulinemic conditions in the CLW and positive control groups than the untreated control group. The increased hepatic insulin sensitivity was associated with enhanced insulin signaling in CLW (pAkt➔pGSK-1β). In conclusion, CLW consumption effectively alleviated diabetic symptoms by improving insulin sensitivity, potentiating hepatic insulin signaling and tightly regulating the insulin secretion capacity in non-obese T2DM rats.
Highlights
Primers were used for detecting rat carnitine palmitoyltransferase (CPT)-1, sterol regulatory element-binding protein (SREBP)-1c, fatty acid synthase (FAS), peroxisome proliferator-activated receptor (PPAR)-γ, Sirtuin (SIRT)-1 and β-actin genes as previously described [19]
After measuring lysate protein contents with a Bio-Rad protein assay kit (Hercules, CA, USA), lysates with equivalent protein contents (30–50 μg) were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by immunoblotting with antibodies to phosphorylated Aktser478, Akt, phosphorylated glycogen synthase kinase (GSK)-3β, GSK-3β, phosphorylated AMP Kinase (AMPK), AMPK, phosphoenolpyruvate carboxykinase (PEPCK) and β-actin (Cell Signaling Technology, Beverly, MA, USA), [23,24]
Akt and GSK phosphorylation, which are important for regulating hepatic insulin signaling, were slightly attenuated in the untreated control group compared to the cPyubolifshCedod: 1onNoopvseims blaern2c0e1o7lata water extract (CLW)-H and positive control (Figure 5)
Summary
Type 2 diabetes is known to develop as a consequence on insulin secretion not compensating for Tyinpseul2indrieasbisettaensceis[1k]n; hoowwnevtoerd, tehveeplorepciasse amceochnasneiqsumebnycewohnichintshueliimn pseaicrrmeteinotnonf tohteccoommppeennssaattiionng for insulinleraedssisttoantycpee[12]d; hiaobwetesveisr,utnhceleparre. cTishee mmeacjohrapnaitshmwbayyswlehaidcihngthteo itmyppea2irdmiaebnetteosf athree dcioffmerpeennt sination leads tAostiyapnes 2adndiabCeateuscaisiuansc.leTahr.eThInetemrnaajotironpaalthDwiabyestelesadFiendgertaotitoynpeh2asdiraebpeotretsedarethdaitffethrenret iwn eAresians and Ca1u13c,a9s0i0a,n00s0. Animal models for Asian type 2 diabetes should be non-obese and have an insulin secretion capacity that is incapable of maintaining normoglycemia concurrent with insulin resistance [3]. Partial pancreatectomized (Px) rats meet these criteria for Asian type 2 diabetes [4] They are non-obese and have about 50–60% of the insulin secretion capacity of normal rats, and they show almost normal fasting serum glucose levels and slightly higher post-prandial serum glucose levels [4]. CLW significantly improves anti-adipogenic activity and dyslipidemia in diet-induced obese rats [10]. The isolated effective components of CLW have not been studied for their efficacy for treating metabolic diseases; the saponins, flavonoids and inulin in CLW may have a hypoglycemic effect by potentiating insulin secretion and improving insulin resistance. The anti-diabetic mechanisms of action of CLW were explored by evaluating its ability to normalize insulin sensitivity and secretion
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