**2. Therapeutic targets for type 2 diabetes mellitus**

As type 2 DM is a progressive disorder, the search for effective treatments is essential to maintain hyperglycemia and its associated diabetic complication. Insulin resistance and impaired beta-cell function lead to hyperglycemia due to alteration in glucose homeostasis, which in turn cause loss of postprandial glucose control. Therefore, postprandial blood glucose maintenance is essential to manage the hyperglycemic condition and associated complications in type 2 diabetes patients [8]. Postprandial hyperglycemia in type 2 DM patients can be controlled by inhibiting metabolic enzymes such as α-amylase, α-glucosidase, dipeptide peptidase-IV, gut-derived peptide hormones (incretins), and glucagon-like peptide-1 hormone. The glucose-dependent insulinotropic peptide, aldose reductase, angiotensin-converting enzyme, and protein tyrosine phosphatase 1B are involved with diabetic complications [9].

Alpha-amylase and alpha-glucosidase are exo-acting glycoside hydrolase enzymes involved in carbohydrate digestion. Alpha-amylase is involved in the digestion of long-chain carbohydrates, while alpha-glucosidase catalyzes the end step hydrolysis of starch or disaccharides into simple glucose units. Therefore, inhibitors of these enzymes delay glucose absorption, reducing the postprandial blood glucose level [10].

Dipeptide peptidase-IV is a protease enzyme involved in the degradation of incretins, a group of metabolic hormones that stimulate ß cells of Langerhans' islet to release insulin. Incretins are released after nutrient intake, and they delayed gastric emptying and decrease glucagon secretion in addition to stimulation of insulin secretion [11]. Contrarily, the incretin effect on insulin secretion gradually decreases once the patient becomes euglycaemic [12]. Hence, inhibitors of dipeptide peptidase IV are efficient therapeutic means to reduce the degradation of incretins, which help maintain hyperglycemic conditions in type 2 DM.

#### *Advanced Pharmacological Uses of Marine Algae as an Anti-Diabetic Therapy DOI: http://dx.doi.org/10.5772/intechopen.96807*

Similarly, aldose reductase is a rate-limiting enzyme involved in the polyol pathway, which catalyzes glucose reduction into sorbitol in an NADPHdependent pathway. As the aldose reductase has broad substrate specificity, it binds with glucose and converts it into sorbitol once the hexokinase is saturated and the blood glucose level is high. As a result, produced sorbitol is accumulated within the cells and creates an osmotic effect, leading to cataracts and diabetic neuropathy [13, 14]. Thus, aldose reductase inhibitors prevent secondary diabetes complications.

Similarly, the angiotensin-converting enzyme plays a vital role in the renvital angiotensin-aldosterone system, a hormone system responsible for maintaining the blood pressure and fluid balance in the body. Angiotensin-converting enzymes convert angiotensin I into angiotensin II, a potent vasoconstrictor that mainly acts on arterioles that stimulate the release of aldosterone from the renal cortex and improve sodium reabsorption from the kidney. Therefore, activation of the renin-angiotensin-aldosterone system leads to increased blood pressure, resulting in microvascular and macro-vascular complications in patients with type 2 DM. Thus, inhibitors of the angiotensin-converting enzyme reduce the long-term microvascular and macrovascular complications by lowering the arterial and venous blood pressure [15]. A study reported by Ustundag et al. [16] confirms that angiotensin-converting enzyme activity is increased in diabetic patients compared to normal individuals.

Correspondingly, protein tyrosine phosphatase IB (PTP IB) is a negative regulator of the insulin signaling pathway that dephosphorylate tyrosine residues in insulin receptor and insulin receptor substrate-1. Which in turn reduces insulin sensitivity [17]. Hence, inhibition of the PTP IB enzyme leads to lower blood glucose levels by enhancing insulin sensitivity. The stable hyperglycemic condition in type 2DM patients leads to the accumulation of advanced glycated end products in various tissues resulting in diabetic complications such as neuropathy, nephropathy, retinopathy, and other chronic diseases [18]. Therefore, the natural compounds, which inhibit the formation of advanced glycation end products, would be a promising therapeutic target to suppress the diabetic complications associated with glycated products.
