Jelena Aramabašić Jovanović,* Mirjana Mihailović, Aleksandra Uskoković, Nevena Grdović, Svetlana Dinić, and Melita Vidaković
Abstract
Diabetes mellitus is a life-threatening multifactorial metabolic disorder characterized by high level of glucose in the blood. Diabetes and its chronic complications have a significant impact on human life, health systems, and countries’ economies. Currently, there are many commercial hypoglycemic drugs that are effective in controlling hyperglycemia but with several serious side-effects and without a sufficient capacity to significantly alter the course of diabetic complications. Over many centuries mushrooms and their bioactive compounds have been used in the treatment of diabetes mellitus, especially polysaccharides and terpenoids derived from various mushroom species. This review summarizes the effects of these main mushroom secondary metabolites on diabetes and underlying molecular mechanisms responsible for lowering blood glucose. In vivo and in vitro data revealed that treatment with mushroom polysaccharides displayed an anti-hyperglycemic effect by inhibiting glucose absorption efficacy, enhancing pancreatic β-cell mass, and increasing insulin-signaling pathways. Mushroom terpenoids act as inhibitors of α-glucosidase and as insulin sensitizers through activation of PPARγ in order to reduce hyperglycemia in animal models of diabetes. In conclusion, mushroom polysaccharides and terpenoids can effectively ameliorate hyperglycemia by various mechanisms and can be used as supportive candidates for prevention and control of diabetes in the future.
1. Introduction
Diabetes mellitus, characterized by hyperglycemia (abnormally elevated fasting and postprandial glucose level in the blood), represents a heterogeneous group of disorders of multiple etiologies and a major health problem worldwide. While great effort has been made in the management of diabetes, its prevalence continues to grow together with a serious increase of morbidity and mortality related to the development of diabetic complications [1]. While chemical and biochemical hypoglycemic agents, e.g., insulin, tolbutamide, phenformin, troglitazone, rosigitazone, and repaglinide, are the mainstay of treatment of diabetes and are effective in controlling hyperglycemia, they have harmful side-effects and fail to significantly alter the course of diabetic complications [2]. Mushrooms, traditionally used as remedies for diabetes healing, represent an exciting field for developing new types of therapeutics to control diabetes and its complications. Some mushrooms have demonstrated clinical and/or experimental control of blood glucose and modification of the course of diabetic complications without side-effects [3,4]. To date, more and more bioactive components including polysaccharides and their protein complexes, dietary fibers, terpenoids, and other compounds extracted from fruiting bodies, cultured mycelium, or cultured broth of medicinal mushrooms have been reported to have anti-hyperglycemic activity. These compounds exhibit their antidiabetic activity via different mechanisms. However, there is insufficient scientific or clinical evidence to draw definitive conclusions about the efficacy and safety of individual medicinal mushrooms or their isolated bioactive compounds to be used as official drugs for treatment of diabetes. Therefore, well-designed randomized controlled trials with long-term consumption are needed to guarantee the bioactivity and safety of mushroom products for diabetic patients. This review covers contemporary drug therapy for diabetic patients and underlines recent studies that demonstrated the hypoglycemic effect of mushroom major bioactive components as well as the importance of their use in the treatment of diabetes. In addition, known mushroom bioactive component-induced mechanisms and pathways involved in lowering blood glucose concentration are elaborated.
2. Diabetes—Sweet and Silent Killer but Not Unbeatable
Diabetes is life threatening and one of the most common chronic diseases worldwide that has reached alarming levels. Today, according to the International Diabetes Federation nearly half a billion people are living with diabetes worldwide. This number is predicted to increase dramatically, reaching 578 million by 2030, and 700 million by 2045 [5], confirming that diabetes is one of the fastest growing global health problems nowadays.
Diabetes mellitus is a long-term metabolic disorder characterized by elevated blood glucose concentration that results from absolute insulin deficiency or insufficient insulin secretion and/or insulin sensitivity [6]. According to Schmeltz and Metzger [7], a new classification of diabetes relies on etiology and pathophysiology, without distinction regarding age of onset or type of treatment. The main categories of diabetes are type 1, type 2, double (hybrid), and gestational diabetes mellitus.
Type 1 diabetes results from autoimmune destruction of the pancreatic β-cells [8,9], which usually leads to absolute insulin deficiency. Patients with this type of diabetes require insulin therapy to maintain normoglycemia and a healthy lifestyle to manage their condition effectively [10]. Type 1 diabetes which usually affects children or young adults accounts for 5–10% of the total diabetic population.
Type 2 diabetes may range from predominant insulin resistance with relative insulin deficiency to a predominantly insulin secretory defect with insulin resistance [10]. This type of diabetes is most commonly seen in older adults and accounts for 90–95% of the total diabetic population. The major risk factors for type 2 diabetes are family history of diabetes, age, obesity, unhealthy diet, ethnicity, and physical inactivity [11]. Nowadays, type 2 diabetes can be increasingly seen in children, adolescents, and younger adults due to an unhealthy way of life. The symptoms are often unobvious because the blood sugar is not high enough to be noticed. In most cases, the disease is diagnosed many years later when hyperglycemia together with macrovascular and microvascular complications becomes apparent.
Since precise definition and diagnosis of type 1 and type 2 diabetes has become more difficult and very challenging, a new category of diabetes termed double or hybrid diabetes has been introduced. Double diabetes possesses symptoms of both type 1 and type 2 diabetes including obesity, insulin resistance, type of latent autoimmune diabetes in youth (LADY) autoantibodies (namely GAD56, IA2), and insulin antibodies [12].