Kuracloud Endocrine PDF

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Endocrine...

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The Endocrine System The endocrine system consists of a number of specialised tissues and organs located throughout the body (Fig. 1.1), which secrete hormones that target one or more tissues to regulate cell function, blood levels of macronutrients (carbohydrates, glucose, proteins etc.) and small ions and molecules (calcium, phosphate, small polypeptides etc.) amongst other functions. Hormones also play a vital role in controlling growth and reproduction, as well as responses to stress. Some key properties of hormones are:  Secreted hormones produced in an endocrine organ have effects on distant organs (Fig. 1.2).  Affect all target tissues in the body at once.  Often feedback systems for regulation, some examples are follicle stimulating hormone (FSH), oestrogen, growth hormone (GH), and insulin. There are three different types of hormones found in the body: 1. Steroid hormones 2. Peptide hormones 3. Amines See your lectures and textbook for detailed information on all three groups. Fig 1.2 Most common cellular responses to hormone action.

Endocrine Feedback Mechanisms In the body, many systems are homeostatically maintained by feedback mechanisms, this is especially the case in the endocrine system. Feedback can be either positive or negative; however, negative feedback is the most prominent. In endocrine physiology, feedback mechanisms are critical in maintaining blood concentration levels of a given hormone, to mediate a desired effect. For example, during childbirth oxytocin is released from the posterior pituitary in response to the foetuses head pushing against the cervix. Oxytocin is a powerful smooth muscle contractor, causing an increase in uterine contractions. As the baby's head moves further down, this triggers more oxytocin release, therefore, stronger uterine contractions. This is an example of positive feedback. More commonly though, is negative feedback, where the release of a hormone triggers its "switching off" (as opposed to an increased production as described above for oxytocin). Examples of some important endocrine negative feedback mechanisms are shown in Fig. 1.3 below.

Fig 1.3 Examples of negative feedback. (A) The production of thyroid releasing hormone (TRH) form the hypothalamus acts on the anterior pituitary to trigger the release of thyroid stimulating hormone (TSH). TSH acts on the thyroid gland to trigger the release of thyroid hormone (T3 and T4). The release of thyroid hormone negatively (-) feeds back to the anterior pituitary and the hypothalamus to inhibit TSH and TRH secretion, respectively. (B) A similar process is involved for the secretion of cortisol from the adrenal gland. Corticotropin-releasing hormone (CRH) is released from the hypothalamus, where it acts on the anterior pituitary to trigger the release of adrenocorticotropic hormone (ACTH), which acts on the adrenal gland to trigger cortisol release. An increase in cortisol negatively feeds back on the anterior pituitary and hypothalamus to inhibit its own secretion.

Regulation of Blood Glucose Glucose is essential for the normal functioning of the human body. It is the main simple carbohydrate (monosaccharide) used by our body as a fuel source and it must be maintained within a normal range. The absorption of digested nutrients can alter circulating blood glucose concentration. Blood glucose homeostasis is maintained primarily by two hormones, insulin and glucagon. Variation in the secretion of these hormones in response to changes in blood glucose concentrations underpins blood glucose homeostasis. Insulin and glucagon are released from specialised cells found in the Islets of Langerhans of the pancreas. An increase in blood glucose concentration will stimulate the release of insulin, a peptide hormone, from pancreatic β-cells into the circulation. Insulin will bind to insulin surface receptors of adipocytes, myocytes and hepatocytes. This will result in changes in intermediary metabolic pathways as well as changes in glucose membrane permeability. The net result is restoration of glucose levels. A decrease in blood glucose will trigger the release of the peptide hormone glucagon from pancreatic α-cells into the circulation. Similar to insulin, glucagon will bind to surface receptors to alter intermediary metabolic pathways (Figure 1.4). Glucagon acts mainly on hepatocytes to increase blood glucose concentration.

© Figure 1.4. A diagram showing the body's normal response to increased or decreased blood glucose concentrations.

Blood glucose concentration can also be increased by other hormones and the autonomic nervous system. The other hormones that are known to increase blood glucose levels are known as the counter-regulatory hormones. They include adrenaline, cortisol and somatotropin (growth hormone). These hormones activate enzymes which convert other substrates to glucose or reduce insulin’s

effectiveness at the receptor level, promoting insulin resistance/impaired glucose tolerance. Several gastrointestinal hormones can also affect blood glucose concentrations by their ability to stimulate insulin secretion in response to food. They are known as incretins and include glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 1 (GLP1). These hormones facilitate the uptake of glucose by muscle and the liver while simultaneously suppressing glucagon secretion. There is only one way, however, to lower blood glucose concentration and that is through insulin.

Metabolic Changes During Fasting The body is able to maintain normal blood glucose concentrations for prolonged periods of fasting. This homeostatic ability ensures that a continuous supply of glucose is available to tissues. This is particularly important for the brain as it utilises glucose as its main fuel source. The other organs within the body are able to meet their energy requirements during fasting using a variety of body stores. When an individual has not consumed any food for an extended period of time, the blood glucose concentration will start to decrease. Falling blood glucose will feedback to the pancreas resulting in a decrease in insulin secretion by the β cells. At the same time, glucagon will be released from the α cells in the Islets of Langerhans of the pancreas. The other counter-regulatory hormones (adrenaline, cortisol and somatostatin) will also contribute to help restore blood glucose to its normal concentration. The principal target for glucagon is the liver. In response to glucagon, the liver will increase glucose production through glycogenolysis and gluconeogenesis (Figure 1.5). Insulin, on the other hand, stimulates the liver to store glucose in the form of glycogen. Glucagon is also important in the regulation of adipose metabolism. Upon fasting, glucagon will act on adipocytes to increase lipolysis. In lipolysis, triacylglycerols are broken down into fatty acids and glycerol which are then mobilised into the circulation. The glycerol is fed into the glucogenesis pathway, while the fatty acids can be used to generate ketone bodies (ketogenesis) in the liver (Figure 1.5). These ketone bodies can be utilised by most tissues as an alternate fuel source.

© Figure 1.5. How the body maintains glucose homeostasis during periods of fasting.

Absorption of Glucose Absorption of glucose into the bloodstream mostly occurs in the duodenum. Glucose must first pass through the upper gastrointestinal system before it can enter the lumen of the duodenum. During this time, pure glucose, such as what you will be consuming in the practical, does not undergo any digestion as it is a monosaccharide already in its simplest form. Once glucose has reached the lumen of the duodenum it will be transported across the epithelium and into the circulation. The epithelial cells of the duodenum contain the Na+/Glucose co-transporter (SGLT) on their luminal, or apical, membrane and the Na+/K+ ATPase pump on the basolateral membrane. The Na+/K+ ATPase actively transports Na+ out of cell and into the interstitial space decreasing the intracellular Na+ concentration (Figure 1.6). This generates a gradient across the luminal membrane that provides the diffusion force for the passive movement of Na+ into the cell. The diffusion force can then be utilised to co-transport glucose into the cell (secondary active transport). Glucose will be transported out of the cell across the basolateral membrane into the interstitial space via facilitated diffusion through the glucose transporter 2 (GLUT2). It then makes its way into the capillaries down its concentration gradient (Figure 1.6). For glucose metabolism to occur, glucose must be transported across the cell membrane. In skeletal muscle, GLUT4 is the necessary transporter. Both insulin and exercise increase the uptake of glucose into skeletal muscle.

© Figure 1.6. Glucose being absorbed into the bloodstream from the lumen of the duodenum.

Oral Glucose Tolerance Test (OGTT) A glucose load produces a rise in blood glucose concentration which returns to normal in healthy individuals within two to three hours by insulin promoting glucose uptake into the tissues, especially into muscle and adipose tissue (the so-called "peripheral utilisation of glucose"). An oral glucose tolerance test (OGTT) is a diagnostic test usually used to quantify how your body is able to tolerate a known oral load of glucose. This can be a useful tool in identifying insulin resistance/impaired glucose tolerance, and can indicate an underlying pathology such as diabetes mellitus, if blood glucose levels are not maintained within the normal range. An OGTT involves the ingestion of 75 g of glucose. Blood glucose levels are monitored over a 2 hour period, and are measured at regular intervals (Table 1.2). In this practical, you will fast for an 8 hour period and measure your blood glucose levels every 30 min after consuming a 75 g glucose drink. In both tests, urine is tested for glucose at fasting and 1 hour postprandial. Table 1.2 Blood glucose concentrations (mmol/L) in venous blood after consumption of 75 g of glucose in solution (Australian Government, National Health and Medical Research Council, 2009)

Fasting 120 min

Normal non-pregnant

Impaired fasting glucose

Diabetes mellitus...