CHAPTER 1

INTRODUCTION

1.1 Diabetes Mellitus

Diabetes Mellitus is a group of metabolic disorders which is characterized by chronic hyperglycemic condition with elevated blood glucose levels (Kohei., 2010). It may be either impaired insulin production or inability of cells to respond properly to the insulin synthesized from beta cells (Rudolf et al., 2012). There are majorly two types of diabetes- Type I or Insulin Dependent Diabetes Mellitus and Type II or Non-Insulin Dependent Diabetes Mellitus.The later condition is characterized by fasting hyperglycemia along with a risk of thrombolytic and atherosclerotic disorders that mainly affect the cerebral, peripheral and coronary arterial trees (Grant., 2007). Diabetes is associated with various complications including micro vascular and macro vascular complications such as retinopathy, nephropathy, atherosclerosis, endothelial dysfunction and erectile dysfunctions.

1.1.1 Type-I Diabetes (IDDM or Juvenile onset Diabetes Mellitus)

Type I is a form of diabetes mellitus that results from the autoimmune destruction of the insulin-producing beta cells in thepancreas The ultimate lack of insulin leads to enhanced blood and urine glucose. The hallmark symptoms are polyuria (frequent urination), polydipsia (increased thirst), polyphagia (increased hunger), and weight loss. The reason of diabetes mellitus type 1 is unknown. Type 1 diabetes can be distinguished from type 2 by autoantibody testing. TheC-peptide assay can also be used to measure endogenous insulin production. Global the number of people with DM type 1 is unknown. It is estimated that about 80,000 children developed the disease a year. Numbers of people who currently have the disease in the United States are possibly as much as three million. Rates varies from a low of 1 per 100,000 in Japan and China to 8 to 17 per 100,000 in Northern Europe and the U.S., to a high of about 35 per 100,000 in Scandinavia

• Caused by immune destruction of beta cells of the pancreas.
• Antibodies to islet cells and insulin are observed at diagnosis.
• Insulin secretion gradually decreases.
• May present at any age but most common in childhood and adolescence. Insulin by sc injection is necessary for survival.
• Contributing factors:- Genetic predisposition, Environmental trigger (infection or stress)

1.1.2 Type- II Diabetes (NIDDM or Adult onset Diabetes Mellitus)

Type II diabetes may be caused either by insulin resistance in the liver and skeletal muscle, or enhanced glucose production in liver, or excess production of free fatty acids by fat cells and insulin deficiency.

• Insulin secretion diminishes with gradual beta cell failure.
• Reductions in blood glucose levels can be achieved with changes in food intake and also physical activity patterns. Oral medication and/or insulin injections are finally required.

Contributing factors:

• Obesity
• Age (onset of puberty is associated with increased insulin resistance)
• Lack of physical activity
• Genetic predisposition
• Racial/ethnic background (Native American, African American Hispanic and Pacific/Asian Islander)
• Conditions associated with insulin resistance as in polycystic ovary syndrome

1.2 Penile Anatomy

The penis composed of three bodies of erectile tissue which run in parallel; the corpus spongiosum, surrounding urethra and terminating in glans penis and the two corpora cavernosa (CC) function as blood-filled capacitors which provide structure to the erect organ (Andersson et al., 1995). The penile CC is highly organised vascular structures which are morphologically acclimatised to their function of becoming engorged of sexual arousal. The trabecular smooth muscle comprises approximately 40-50% tissue cross-sectional area, as evaluated by histomorphometric analysis (Nehra et al., 1998). There are three main arteries in penis ie, cavernosal, dorsal and bulbourethral. These three arise from a shared branch of internal pudendal artery and provide an immense anastomotic network (Tiee et al., 2010). Nowadays, there is a tendency to Role of Arginase Inhibitor and Alpha-Tocopherol in Streptozotocin Induced Sexual Impairment in Male Rats 2013-14 perform experiments using pudendal artery in vitro instead of cavernosal tissue to check pathophysiological aspects of ED as this artery is the vital resistance of penile engogerment during sexual stimulation. Novel research suggests that pudendal artery contributes about 70% of total penile vascular resistence (Manabe et al., 2000). The blood supply in CC is mainly fed from the penile cavernosal artery (Andersson et al., 1995) which causes corporal engorgment during erection, whereas deep dorsal artery causes glans enlargement but venous drainage is not similar to the arterial supply; there has only one deep dorsal vein which runs alongside dorsal arteries and nerves in the Buck’s fascia above the tunica albuginea which is a multilayered organized structure where emissary veins pass. The penile venous system is generally stated as a single deep dorsal vein along with a pair of dorsal arteries located between tunica albuginea and Buck’s fascia for venous drainage (Moscovici et al., 1999). The corpus spongiosum which is erectile tissue analogous to CC but with thinner tunica albuginea. The urethra lies inside the spongiosum. The innervations of penis is both autonomic ie, sympathetic and parasympathetic and somatic ie, sensory and motor. From the neurons present in the spinal cord & peripheral ganglia, the sympathetic with parasympathetic nerves merge to form cavernous nerves, which enter in CC and corpus spongiosum for affecting the neurovascular events during detumescence and tumescence (Dean et al., 2005).

1.3 Physiology of Penile Erection

Penile erection involves central and peripheral pathways. Tumescence initiated after central integration and processing of visual, tactile, olfactory and imaginative stimuli. At the initial of sexual stimulation, signals are generated to peripheral tissues involved. Hence final response is mediated by coordinating spinal activity through the autonomic pathways to penis, and also in somatic pathways to perineal striated muscles. Both of the central and peripheral regulation of the PE involves several neurotransmitters, of which details are still incompletely known. Spinally, there may be a network consisting of the primary afferents from the genitals along with spinal interneurons, sympathetic, parasympathetic and (somatic) nuclei, which is capable to integrate all information. Peripherally, a balance between substances which control the degree of contraction of cavernosal smooth muscle determining the functional state of the penis (Gratzke et al., 2010). The dynamic interplay between vasoconstrictors and vasodilators within the penis establish the state of erect or flaccid. PE is determined by the pressure changes in cavernosal arterioles and sinuses. The vasculature nature of the erectile mechanism differs from most of the vascular beds as it is comprised of arterioles and hollow blood-filled sinuses, both that are lined with endothelial cells and smooth muscle (Dean et al., 2005) as previously described. During flaccidity, this tissue is tonically contracted which allow only a small amount of arterial flow regarding nutritional purposes. Partial pressure of oxygen (PO2) in blood is around 35mmHg (Sattar et al., 1995). On the other hand, dilation of penile arteries is the primary event in the consequence of erection