Jerusalem artichoke is high in fructoligosacharides whereas chungkookjang is rich in isoflavonoid aglycones and small peptides. Large dosages of chungkookjang reportedly exert anti-diabetic effects by potentiating glucose-stimulated insulin secretion and attenuating insulin resistance [5, 7]. In addition, Jerusalem artichoke had anti-diabetic effects due to high in fructoligossacharides that may decrease insulin resistance by mechanisms that remain unknown. Since chungkookjang and Jerusalem artichoke may have different anti-diabetic mechanisms it is worth evaluating their combined effects. In the present study, HTL and CKJ improved glucose tolerance differently in diabetic rats, and when combined they remarkably enhanced glucose homeostasis in Px rats, type 2 diabetic rats. After removing 90% of the pancreas, the pancreas is regenerated up to 40-50% of the intact pancreas and insulin secretion capacity is about 50-60% of the non-diabetic rats. Thus, Px rats are non-obese and moderate type 2 diabetic animal model. Px rats exhibited a similar phenotype to Asian type 2 diabetes, which has specific characteristics of non-obesity and high susceptibility to insulin deficiency with increased insulin resistance [14–16]. Rather than becoming hyperglycemic, Asians with insulin resistance exhibit normal insulin levels or hypoinsulinemia, and easily progress from glucose intolerance to type 2 diabetes . Px rats are a good model to study β-cell expansion and the relationship between β-cell function and insulin resistance since they are a non-obese type 2 diabetic model with characteristics relevant to Asian type 2 diabetes.
HTL contains fructan which is largely comprised of inulin and oligofructose. Fructan is a non-digestible fiber with health benefits [23–25]. It selectively stimulates the growth and/or activity of some beneficial bacteria in the colon and represses the growth of pathogens . However, the effects of inulin and oligofructose on glucose metabolism are not fully understood and the available data are contradictory. Recently, Dewulf et al. [26, 27] revealed that inulin-type diets counteract high-fat diet-induced obesity via suppressing G protein-coupled receptor-43 overexpression through the modification of the gut microbiota and they resulted in a decreased level of circulating lipopolysaccharide and lower C-reactive protein levels to attenuate inflammation. Therefore, the prebiotics such as oligofractan in HTL might reduce systemic inflammation which could be protective against diabetes. Since CKJ contains beneficial Bacillus that can use oligofructan in HTL as an energy source, the combination of CKJ and HTL may have a synergistic effect. Some studies have found that in diabetic rats, 10-20% oligofructose diets decrease postprandial glycemia, but the results for serum insulin levels were inconsistent . In healthy humans, 20 g/d oligofructan does not alter fasting serum glucose levels, but in diabetics, 8 g/d oligofructan lowers glucose levels [10, 24]. However, Aslan et al.  found that 80% ethanol extracts (500 mg/kg body weight) did not improve blood glucose levels after glucose load, perhaps due to higher contents of free fructose resulting from improper storage conditions [28, 29]. Improperly stored HTL can break down into simple sugars and exacerbate diabetic symptoms. We found that 5% HTL extracts marginally improved glucose metabolism (data not shown).
Besides lowering postprandial glycemia, oligofructan reduces hepatic gluconeogenesis in normal subjects , which may be mediated by short-chain carboxylic acids, especially propionates, made by intestinal microbes from inulin. Boillot et al.  reported that propionate consumption reduced fasting blood glucose levels in rats. In addition, propionates inhibit gluconogensesis in isolated hepatocytes when converted into methyl malonyl CoA and succinyl CoA which inhibit pyruvate carboxylase activity. In consistent with other study about oligofructans , the present study revealed that HTL improved hepatic insulin sensitivity by enhancing insulin signaling in the liver.
Oligofuctose was shown to increase serum glucose dependent insulinotropic peptides and glucagon-like peptides (GLP-1), regulating post-prandial insulin release and potentiating insulin action by two-fold in rats . However, it is controversial. Parnell and Reimer  reported that oligofructan supplementation (21 g/day) for 12 weeks decreased body weight by lowering food intake and serum glucose levels in obese adults but serum GLP-1 levels were not altered. The increased serum GLP-1 levels by oligofructans might be related to the tropic action of short-chain fatty acids produced by colonic oligofructan fermentation. However, in the present study HTL did not change glucose-stimulated insulin secretion and β-cell mass in diabetic rats, but HTL+CKJ additively improved insulinotropic action suggesting that HTL may have enhanced the action of chungkookjang. Thus, the anti-diabetic effects of HTL were related to enhanced insulin signaling decreasing hepatic gluconeogenesis, probably due to fructan in HTL. The different results may be due to the amount of oligofructan contents in the HTL diet. However, we cannot eliminate the possibility of stronger anti-diabetic effects with higher dosages of oligofructan from Jerusalem artichoke.
We previously demonstrated that chungkookjang exerts insulinotropic action, potentiating glucose-stimulated insulin secretion and increasing β-cell mass by elevating β-cell proliferation and decreasing apoptosis . GLP-1 secreted from the intestinal L-cells increases insulin secretion from β-cells and expands β-cell mass after meals. GLP-1 or exendin-4, a GLP-1 receptor agonist, potentiates insulinotropic action by enhancing insulin/IGF-1 signaling in β-cells through increasing intracellular cAMP→ phosphorylation of cAMP responding element binding protein (CREB) →IRS-1 protein expression [32, 33]. Genistein enhances insulinotropic action in β-cells by activating cAMP→CREB phosphorylation→ tyrosine phosphorylation of IRS2 [34, 35]. In addition, isoflavnoids support glucose management through estrogen-like actions. Estrogen is reported to improve glucose homeostasis by potentiating glucose-stimulated insulin secretion and attenuates insulin resistance .
Soy protein also limits the accretion of visceral adiposity and increased peroxisome proliferator-activated receptor (PPAR)-γ and GLUT4 expressions, improving glucose metabolism in Wistar rats fed sucrose-rich diets . Soy protein including isoflavonoids partially prevents insulin resistance, steatosis, and hypercholesterolemia in rats fed Western diets by reducing the expression of enzymes related to fatty acid synthesis such as nuclear sterol receptor element binding protein-1c and by increasing the proteins associated with fatty acid degradation such as PPAR-α . However, Gobert et al.  reported that soy protein isolates do not significantly affect fasting or postprandial glucose or insulin, fasting HbA1C, or indices of insulin sensitivity. Thus, it remains unclear if soy protein has anti-diabetic effects. Our previous in vitro study demonstrated that water extracts of chungkookjang, containing mostly peptides, greatly increase insulin-stimulated glucose uptake compared to soybeans by increasing PPAR-γ expression . The increase by water extracts is much greater than the methanol fraction of chungkookjang containing isoflavonoid , suggesting that peptides in chungkookjang are better for improving insulin resistance than those in soybeans.