1. Introduction
The prevalence of type 2 diabetes mellitus (T2DM) is increasing rapidly
worldwide (Rosengren & Dikaiou, 2023). International Diabetes
Federation reported that the number of T2DM patients will probably rise
to 700 million by 2045 (Cucinotta et al., 2021).
Obesity is a high-risk factor for
T2DM, and there is a close link between the two conditions (Kojta,
Chacinska & Blachnio-Zabielska, 2020). In support, the epidemiological
survey has demonstrated that obese patients are more likely to develop
T2DM (Lee, Park & Choi, 2022).
Insulin is a hypoglycemic hormone secreted under endogenous or exogenous
stimulation, which helps to store energy as the form of lipid (Najjar,
Caprio & Gastaldelli, 2023). Nowadays, insulin is losing its
physiological significance in energy storage with abundant nutritional
sources. Conversely, over-nutrition triggers insulin resistance (IR).
Accumulating facts have evidenced that IR plays a pivotal role in
obesity-induced T2DM (Samuel & Shulman, 2012). It has been recognized
that obesity could weakens the metabolic functions of insulin in the
liver, skeletal muscle and adipose tissues, induce triglyceride (TG)
accumulation and β-cells failure, thereby leading to IR and finally T2DM
(Kojta, Chacinska & Blachnio-Zabielska, 2020). Obese patients could
deliver the risk of IR to the next generation as early as pregnant
(Nicholas, Morrison, Rattanatray, Zhang, Ozanne & McMillen, 2016).
Hence, relieving obesity-induced IR is one of the key therapeutic
strategies to improve T2DM.
The most natural and successful
approaches to cure IR and T2DM are changing unhealthy lifestyles, taking
more exercise and keeping on a healthy diet, however, it is hard to
maintain a healthy routine. Gastric bypass surgery or bariatric surgery
could also reduce the blood glucose levels in diabetic patients, but it
sacrifices caloric intake and bodyweight artificially (Sylow, Tokarz,
Richter & Klip, 2021). Insulin sensitizers (biguanides and
thiazolidinediones), nutrient absorption adjustment medicine
(α-glucosidase inhibitors), insulin secretion-promoting medicine
(sulfonylurea) and glucagon-like peptide-1 (GLP-1) agonists medicine are
frequently used to improve T2DM. However, these medicines have limited
efficacy and unsatisfied side effects (Bellary, Kyrou, Brown & Bailey,
2021; Perreault, Skyler & Rosenstock, 2021). For example, metformin, a
first-line drug of biguanides, is forbidden to use in patients with
advanced chronic kidney disease and liver disease. Sulfonylurea
administration might cause hypoglycemia, weight gain, and cardiovascular
disease exacerbation. Therefore, screening for natural medicines with
potent efficacy and few side effects on obesity-induced T2DM are
attracting great attention.
Diabetes mellitus (DM) is named “Xiao Ke” in traditional Chinese
medicine (TCM), it is mandarin, for a general term of a series of
symptoms including polydipsia, polyphagia, polyuria, emaciation, and
sweet urine (Su, Hu, Tang, Tang & Huang, 2023). “Xiao Ke” was
mentioned in the book “Su Wen • Tong Ping Xv Shi Lun(Plain Questions & General Comments )”, which explained that
obesity was a major pathogenic factor in DM and guided the principles of
medication in TCM for diabetes. As
TCM, herbs, and nutraceuticals share a lot of similarities in their
original materials, it makes sense to look for neoteric cures for
diabetes-related disorders in these natural herbs and nutraceuticals
(Fang et al., 2021).
As IR is a multi-factorial etiology disease with complex pathomechanism,
single target therapy is limited for its prevention and treatment.
Recently, natural products from herbs and nutraceuticals have shown
unique characteristics as multi-component and multi-target in improving
IR and T2DM efficiently, which attracts wide attention and favor (Law et
al., 2022). An increasing number of researches have indicated that
active constituents from herbs and nutraceuticals might ameliorate DM
and its complications by improving metabolic abnormalities, inhibiting
inflammation, reversing intestinal flora disorder and regulating miRNAs.
For instance, resveratrol, berberine and curcumin have been proved to
exert anti-diabetic effects through various mechanisms simultaneously
(Kim, Chung & Song, 2019; Kunnumakkara et al., 2017; Xu et al., 2021).
The aim of the present review was to summary the effects of natural
active constituents on IR (especially obesity-induced IR), as well as to
explain and discuss the action mechanisms. This review will provide
potential perspectives for the clinical treatment of IR and T2DM.