Category Archives: Endocrinology (diabetes)

The Hypothalamus and Pituitary Gland, with Animation.

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The hypothalamus and the pituitary gland are at the center of endocrine function. The hypothalamus is part of the brain, while the pituitary, also called hypophysis (hy-POFF-ih-sis), is an endocrine gland. The hypothalamus links the nervous system to the endocrine system via the pituitary gland. The two structures are located at the base of the brain and are connected by a thin stalk.

The hypothalamus produces several hormones, known as neurohormones, which control the secretion of other hormones by the pituitary. Pituitary hormones, in turn, control the production of yet other hormones by other endocrine glands.

The pituitary has two distinct lobes:

The anterior pituitary, also called adenohypophysis (AD-eh-no-hy-POFF-ih-sis), communicates with the hypothalamus via a network of blood vessels known as the hypophyseal portal system. Several neurohormones produced by the hypothalamus are secreted into the portal system to reach the anterior pituitary, where they stimulate or inhibit production of pituitary hormones. Major hormones include:

  • Gonadotropin-releasing hormone, GnRH, a hypothalamic hormone, stimulates the anterior pituitary to producefollicle-stimulating hormone, FSH, and luteinizing hormone, FSH and LH, in turn, control the activities of the gonads – the ovaries and testes.
  • Corticotropin-releasing hormone, CRH,promotes the secretion of adrenocorticotropic hormone, ACTH, which in turn stimulates production of cortisol by the adrenal gland.
  • Thyrotropin-releasing hormone, TRH, promotes the release of thyroid-stimulating hormone, TSH, and prolactin. TSH, in turn, induces the thyroid gland to produce thyroid hormones. Prolactin stimulates the mammary glands to produce milk.
  • Prolactin-inhibiting hormone, PIH, inhibits production of prolactin.
  • Growth hormone–releasing hormone, GHRH, promotes production of growth hormone, or somatotropin, which has widespread effects on the growth of various tissues in the body.
  • Growth hormone–inhibiting hormone, GHIH, or somatostatin, inhibits production of growth hormone.

The posterior pituitary, also called neurohypophysis, communicates with the hypothalamus via a bundle of nerve fibers. These are essentially hypothalamic neurons with cell bodies located in the hypothalamus while their axons EXTENDED to posterior pituitary. These neurons produce hormones, transport them down the stalk, and store them at the nerve terminals within the posterior pituitary, where they wait for a nerve signal to trigger their release. Two hormones have been identified so far:

– Vasopressin, also known as antidiuretic hormone, ADH, acts on the kidneys to retain water.

– Oxytocin causes the uterus to contract during childbirth and stimulates contractions of the milk ducts in lactating women.

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Controle Hormonal do Ciclo Menstrual e Ovulação, com Animação.

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O ciclo menstrual é o termo usado para descrever eventos mensais que ocorrem dentro do corpo das mulheres relativo à preparação para uma possível gravidez. A cada mês, um óvulo é liberado de um ovário no processo chamado ovulação. Ao mesmo tempo, o revestimento do útero engrossa, pronto para a gravidez. Se a fertilização não ocorre, o revestimento do útero é eliminado sob a forma de hemorragia menstrual e o ciclo recomeça.
Um ovário contém centenas de milhares de oócitos primários. Cada um deles está contido em uma estrutura chamada folículo, e nesse estágio – um folículo primordial.
O ciclo menstrual está sob o controle de hormônios secretados pela hipófise e ovários. A hipófise está sob o controle do hipotálamo.
O hipotálamo produz um hormônio chamado hormônio liberador de gonadotrofina ou GnRH. O GnRH estimula o lobo anterior da hipófise (adenoipófise) para secretar o hormônio folículo-estimulante (FSH).
O FSH é transportado pela corrente sanguínea para os ovários e estimula um grupo de folículos à crescer. Esses folículos primordiais se desenvolvem em folículos primários e, então, em folículos secundários. Esses folículos secundários produzem um hormônio chamado estrogênio, o qual atua na estimulação do crescimento do endométrio – o revestimento interno do útero. Os folículos secundários competem entre si e somente um deles sobrevive, se tornando um folículo maduro; os outros atrofiam e morrem.
O aumento do nível de estrogênio também atua no hipotálamo e na adenoipófise para aumentar o nível de GnRH e induzir a produção de um outro hormônio – o hormônio luteinizante (LH). O pico na secreção de LH desencadeia a ovulação – a liberação do óvulo do folículo e ovário. O óvulo é, então, levado à tuba uterina pelas fímbrias.
A fertilização por um espermatozoide, quando ocorre, normalmente acontece na ampola – a maior secção da tuba uterina. Imediatamente, o óvulo fertilizado começa o processo de desenvolvimento enquanto se transporta em direção ao útero. Após 6 dias se torna um blastocisto e é implantado no endométrio do útero.
Enquanto isso, o resto do folículo rompido se torna o corpo lúteo, o qual secreta progesterona. A progesterona estimula ainda mais o desenvolvimento uterino, fazendo um ambiente nutritivo para o embrião durante a gravidez. Na falta da gravidez, o corpo lúteo atrofia e os níveis de progesterona caem. Isso leva a uma ruptura do endométrio; a menstruação começa e o ciclo se repete.
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Control Hormonal del Ciclo Menstrual, con Animación.

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El término ciclo menstrual se usa para describir los eventos mensuales que ocurren dentro del cuerpo de la mujer preparándolo para la posibilidad de embarazo. Cada mes, un óvulo se libera de un ovario en un proceso llamado ovulación. Al mismo tiempo, el revestimiento del útero se engrosa, listo para el embarazo. Si la fertilización no llega a ocurrir, el revestimiento del útero se desprende en forma de menstruación y el ciclo empieza de nuevo.
Un ovario contiene cientos de miles de ovocitos primarios u óvulos inmaduros. Cada uno de ellos está contenido en una estructura llamada folículo, y en este estado – un folículo primordial.
El ciclo menstrual está controlado por las hormonas secretadas por la glándula pituitaria y los ovarios. La pituitaria está controlada por el hipotálamo.
El hipotálamo produce una hormona llamada hormona liberadora de gonadotropina o GnRH. GnRH estimula el lóbulo anterior de la pituitaria para secretar hormona foliculoestimulante – FSH.
FSH viaja por el torrente sanguíneo hasta los ovarios y estimula el crecimiento de un grupo de folículos. Estos folículos primordiales se convierten en folículos primarios y luego en secundarios. Estos folículos secundarios producen una hormona llamada estrógeno que actúa estimulando el crecimiento del endometrio –la capa interna del útero. Los folículos secundarios compiten entre ellos y sólo uno de ellos sobrevivirá y se convertirá en un folículo maduro, los demás se atrofian y mueren.
Los niveles de estrógeno en aumento también actúan en el hipotálamo y la pituitaria anterior para incrementar el nivel de GnRH e inducir la producción de otra hormona – hormona luteinizante – LH. Una oleada de hormona LH provoca la ovulación – la liberación del óvulo desde el folículo y el ovario. Las fimbrias arrastran el óvulo y lo llevan a una de las trompas de Falopio.
La fertilización por el espermatozoide, cuando ocurre, normalmente tiene lugar en la región ampular – la zona más ancha de la trompa de Falopio. El óvulo fertilizado inmediatamente empieza el proceso de desarrollo mientras viaja hacia el útero. Después de seis días se convierte en un blastocisto y se implanta en el endometrio del útero.
Mientras, el resto del folículo roto se ha convertido en un cuerpo lúteo, el cual secreta progesterona. La progesterona estimula un mayor desarrollo uterino convirtiéndolo en un lecho nutritivo para el embrión durante el embarazo. Si no hay embarazo, el cuerpo lúteo se atrofia y los niveles de progesterona disminuyen. Esto lleva a la rotura del endometrio, comienza la menstruación y el ciclo se repite.

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Le Contrôle Hormonal du Cycle Menstruel, avec Animation.

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Le cycle menstruel est un terme utilisé pour décrire des événements qui se produisent tous les mois dans le corps d’une femme en vue de la possibilité d’une grossesse. Chaque mois, un ovule est libéré par un ovaire dans un processus appelé l’ovulation. En même temps, la paroi de l’utérus épaissit, prête pour la grossesse. Si la fécondation n’a pas lieu, la muqueuse de l’utérus est excrété dans saignements menstruels et le cycle recommence.  Un ovaire contient des centaines de milliers d’ovocytes primaires ou des ovules immatures. Chacun de ceux-ci est enfermé dans une structure appelée un follicule, et à ce stade – un follicule primordial. Le cycle menstruel est sous le contrôle des hormones sécrétées par la glande pituitaire, ou l’hypophyse,  et les ovaires. L’hypophyse est lui-même sous le contrôle de l’hypothalamus. L’hypothalamus produit une hormone appelée l’hormone de libération des gonadotrophines ou GnRH. GnRH stimule le lobe antérieur de l’hypophyse de sécréter l’hormone folliculo-stimulante, la FSH. La FSH se déplace dans la circulation sanguine vers les ovaires et stimule le développement d’un certain nombre de follicules. Ces follicules primordiaux se développent en les follicules primaires et puis follicules secondaires. Ceux-ci produisent l’hormone œstrogène qui agit pour stimuler la croissance de l’endomètre – la couche interne de la paroi de l’utérus. Les follicules secondaires sont en concurrence les uns avec les autres et un seul survit et devient un follicule mature, les autres s’atrophient et meurent. L’augmentation du niveau de l’œstrogène agit également sur l’hypothalamus et l’hypophyse antérieure pour augmenter le niveau de la GnRH et induire la production d’une autre hormone – l’hormone lutéinisante (LH). Le pic de LH entraîne la rupture du follicule, et la libération de l’ovule mature par l’ovaire. Ce processus est appelé ovulation. L’ovule est ensuite capturé par le pavillon et emmené dans la trompe utérine. Fécondation par un spermatozoïde, quand il se produit, se déroule habituellement dans l’ampoule – la section la plus large de la trompe de Fallope. L’ovule fécondé commence immédiatement le processus de développement tout en voyageant vers l’utérus. Au bout de 6 jours, il devient un blastocyste et est implanté dans l’endomètre de l’utérus. Pendant ce temps, le follicule vide est devenu un corps jaune qui sécrète la progestérone. La progestérone permet de renforcer davantage la muqueuse utérine en vue d’accueillir un ovule fécondé. En l’absence de fécondation, le corps jaune s’atrophie et le niveau de progestérone tombe. Cela conduit à l’effondrement de l’endomètre, les règles commencent et le cycle se répète.

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Understanding the Menstrual Cycle

Below is a narrated animation about hormonal control of the menstrual cycle. Click here to license this video and/or other gynecology/obstetrics videos on Alila Medical Media website.

The menstrual cycle is a term used to describe monthly events that occur within a woman’s body in preparation for the possibility of pregnancy. Each month, an egg is released from an ovary in a process called ovulation. At the same time, the lining of the uterus thickens, ready for pregnancy. If fertilization does not take place, the lining of the uterus is shed in menstrual bleeding and the cycle starts over.
An ovary contains hundreds of thousands of primary oocytes – immature eggs, or ova. Each of these is enclosed in a structure called a follicle, and at this stage – a primordial follicle.
The menstrual cycle is under control of hormones secreted by the pituitary gland and the ovaries. The pituitary itself is under control of the hypothalamus.
The hypothalamus produces a hormone called the gonadotropin-releasing hormone or GnRH. GnRH stimulates the anterior lobe of the pituitary to secrete follicle-stimulating hormone (FSH).
FSH travels in the bloodstream to the ovaries and stimulates a group of follicles to grow. These primordial follicles develop into primary follicles and then secondary follicles. These produce a hormone named estrogen which acts to stimulate the growth of the endometrium – the inner lining of the uterus. The secondary follicles compete with each other and only one of them will survive and become a mature follicle, the rest atrophy and die.
The increasing level of estrogen also acts on the hypothalamus and the anterior pituitary to increase the level of GnRH and induce the production of another hormone – luteinizing hormone (LH). A surge in LH secretion triggers ovulation – the release of the egg from the follicle and the ovary. The egg is then swept up by the fimbriae (FIM-bree-ee) and taken into the uterine tube.
Fertilization by a spermatozoon, when it occurs, usually takes place in the ampulla, the widest section of the fallopian tube. The fertilized egg immediately begins the process of development while travelling toward the uterus. After 6 days it becomes a blastocyst and is implanted into the endometrium of the uterus.
Female sexual cycle
Fig. 1: Hormonal changes during the ovarian and uterine cycles. Click on image to see it on Alila Medical Media website where the image is also available for licensing (together with other related images and videos).

 

 

 

 
Meanwhile, the left-over of the ruptured follicle has become a corpus luteum which secretes progesterone. Progesterone further stimulates uterine development making it a nutritious bed for the embryo in the event of pregnancy. In the absence of pregnancy, the corpus luteum atrophies and progesterone level falls. This leads to the breakdown of the endometrium, menstruation begins and the cycle starts over.

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How blood glucose is regulated?

Blood glucose levels are regulated by the cells of the pancreatic islets (islets of Langerhans). When glucose level is high (e.g. after a meal), beta cells of the islet release insulin into the bloodstream. Insulin stimulates target cells (e.g. muscle cells) to use glucose as energy source. Insulin also induces liver cells to store glucose in the form of glycogen (this process is called glycogenesis). When glucose levels fall (e.g. in the morning before breakfast), another hormone called glucagon is released by alpha cells of the pancreatic islets. Glucagon acts on liver cells to convert glycogen back to glucose and release it into the bloodstream (this process is called glycogenolysis). 

How glucose induces insulin release in beta cells?

Shortly after a meal, level of glucose in the blood is up. High glucose level stimulates beta cells to secrete insulin into the bloodstream (Fig. 1 and 2).
Glucose induces insulin release in beta cells
Fig. 1: Anatomy of a pancreatic islet (islet of Langerhans): beta cells = blue, alpha cells = red; and an enlarged beta cell (lower panel). Glucose enters beta cell and stimulates exocytosis of vesicles containing insulin. Click on image to see a larger version on Alila Medical Media website where the image is also available for licensing.

 

 

 

Glucose enters beta cell through glucose transporter 2 – GLUT2. Increased intake of glucose => increased production of ATP => ATP/ADP ratio is up => ATP-sensitive potassium channel closed => depolarization of cell membrane => voltage-gated calcium channel opens => increased calcium inside the cell => insulin granule exocytosis.
Glucose-stimulated insulin secretion in beta cells
Fig. 2: Chain of events that lead to secretion of insulin from beta cells. See text for details. Click on image to see a larger version on Alila Medical Media website where the image is also available for licensing.

 

 

 

 

How insulin induces glucose uptake in target cells?

Insulin and glucose travel in bloodstream to reach target organs (e.g. muscles, liver,..). In target organs, insulin induces cells to take up glucose. Insulin binds to insulin receptor on target cell => phosphorylation of cytoplasmic domain of receptor => a cascade of signaling events brings the GLUT4 (glucose transporter 4) to the membrane of the cell => glucose enters target cell through GLUT4.

Insulin signaling pathway
Fig. 3: Insulin signaling in target cell. See text fior details. Click on image to see a larger version on Alila Medical Media website where the image is also available for licensing.

Glucagon

Glucagon is secreted into the bloodstream in response to hypoglycemia  low blood sugar. Glucagon has the opposite effect of insulin, its action increases blood glucose level. Glucagon secretion from alpha cells is suppressed by high level of glucose. Low concentration of glucose => increase level of glucagon. Glucagon stimulates breakdown of glucogen stored in liver cells (hepatocytes) and release of glucose into the blood.

                                                                 >  See all Endocrinology topics 

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Diabetes type 1 and type 2

What is Diabetes?

Diabetes mellitus includes a group of conditions characterized by a high level of blood glucose, commonly referred to as blood sugar. Too much sugar in the blood can cause serious, sometimes life-threatening health problems.

There are two types of chronic (lasts for life) diabetic conditions : type 1 diabetes and type 2 diabetes. Pregnant women may acquire a transient form of the disease called gestational diabetes which usually resolves after the birth of baby. Prediabetes is when your blood sugar is at the borderline : higher than normal, but lower than in diabetics. Prediabetes may or may not progress to diabetes.

Insulin and Metabolism of Glucose

In order to understand diabetes we should first understand glucose metabolism and role of insulin. Carbohydrate (carb) in food breaks down to glucose which is carried by the bloodstream to various organs of the body where it is either consumed as an energy source (e.g. in muscles), or is stored for later use (in the liver). Insulin is a hormone produced by beta cells of the pancreas and is necessary for glucose intake by the target cells. In other words, when insulin is deficient, muscle or liver cells won’t be able to use or store glucose and as a result, glucose will accumulate in the blood (Fig. 1).

How blood glucose is regulated ? A feedback loop is in place to ensure that glucose level in the blood is never too high or too low, i.e. in normal range. Shortly after a meal, level of glucose in the blood is up. High glucose level stimulates beta cells to secrete insulin into the bloodstream. Insulin and glucose travel in bloodstream to reach target organs (e.g. muscles, liver,..). In target organs, insulin induces cells to take up glucose for use as energy or store for later use. As glucose is consumed by target organs, its concentration in the blood goes down and no more insulin is secreted from beta cells, insulin level goes down, glucose is no longer taken into cells, this prevents glucose level from going down further. When blood sugar level is too low (e.g. before meal time), previously stored glucose in the liver is released back into the bloodstream thanks to the action of another pancreatic hormone called glucagon. In short, insulin lowers blood sugar level while glucagon increases it. Regulation and ratio of these two hormones are vital for maintaining blood glucose levels within normal range.

> Read more about how glucose induces insulin release in beta cells and how insulin induces glucose uptake in target cells. 

Type 1 and type 2 Diabetes

Type 1 diabetes = insulin dependent : The pancreas does not produce enough insulin due to lack of beta cells. Not enough beta cells in the pancreas => not enough insulin => organs can not use or store glucose => glucose accumulates in the bloodstream. Type 1 is characterized by early (juvenile) onset, symptoms commonly start suddenly and before the age of 20. Type 1 diabetes is normally managed with insulin injection.
Type 1 diabetes
Fig. 1: Type 1 diabetes. The pancreas produces less insulin, liver and muscle cells absorb less glucose, glucose stays in the blood, blood sugar level increased. Click on image to see a larger version on Alila Medical Media website where the image is also available for licensing.

 

 

 

 

 

Type 2 diabetes = insulin resistant : Insulin is produced normally by the pancreas, but for some reasons, the cells of target organs (e.g. muscles, liver,..) do not response to insulin and therefore can not use or store glucose, glucose accumulates in the blood (Fig. 2). Type 2 is characterized by adult onset, symptoms usually appear gradually and start after the age of 30. Type 2 diabetes accounts for about 80-90% of all diabetics. Management focuses on weight loss and includes a low-carb diet.
Type 2 diabetes
Fig. 2: Type 2 diabetes. The pancreas produces the same amount of insulin but organs are unresponsive, glucose can not be used and stays in the blood, blood sugar level increased. Click on image to see a larger version on Alila Medical Media website where the image is also available for licensing.

 

 

 

                                                                                 > Causes and Symptoms

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Diabetes causes and symptoms

 Overview of Diabetes type 1 and type 2 < PREVIOUS

Causes


Causes are very different for each case as diabetes is a group of diseases that share the same outcome : high blood sugar. As the process of blood sugar control  is complex and involves many steps, anything that goes wrong at any step would result in the disease (Fig. 1).
Insulin action and diabetes type 1 and 2
Fig. 1: Type 1 and 2 diabetes. In healthy people (upper panel), pancreas produces enough insulin, insulin binds to receptor on target cell and induces glucose intake. In type 1 diabetes (middle panel) insulin production is reduced, less or no insulin binds to receptor, glucose stays outside target cell (in the blood). In type 2 diabetes (lower panel) pancreas produces enough insulin but something goes wrong either with the receptor binding or insulin signaling in the target cell, glucose stays outside the cell (in the blood). Click on image to see a larger version on Alila Medical Media website where the image is also available for licensing.

 Causes of type 1 diabetes: In type 1 diabetics, beta cells of the pancreas are destroyed by the immune system by mistake – autoimmune disease (Fig.2). The reason why this happens is unclear, but genetic factors are believed to play a major role.

Pancreatic islet normal and type 1 diabetic
Fig. 2: Anatomy of a pancreatic islet showing beta cells selectively destroyed in type 1 diabetes. Click on image to see a larger version on Alila Medical Media website where the image is also available for licensing.

 

 

 

Causes of type 2 diabetes: These are more diverse as there are many steps that could possibly go wrong. In some cases, beta cells are dysfunctional and produce a modified version of insulin that can no longer bind to its receptor. In other cases, the problem lies within insulin receptor or in the downstream signaling in target cells. The common hallmark is the normal level of insulin in the blood. Here again, genetic factors predispose susceptibility to the disease, but it’s believed that lifestyle plays a very important role. Typically, obesity, inactive lifestyle, and unhealthy diet are associated with higher risk of type 2 diabetes. 

Causes of gestational diabetes: hormonal changes during pregnancy, notably the presence of placental hormone lactogen, may interfere with insulin receptor on target cells and make them less responsive to insulin. This occurs in about 5 to 10% of all pregnancies, more commonly during the third trimester, and if left untreated, may progress to type 2 diabetes.

Symptoms

Type 1 symptoms tend to come sudden, quickly, type 2 symptoms may develop over a long period of time. The earliest signs of diabetes are excessive thirst, frequent urination, then come excessive hunger, fatigue, weight loss, high blood pressure, blurred vision, frequent infections (especially in the skin, genitals, bladder). Long term untreated diabetes may lead to other complications including vascular diseases (heart attack, stroke), nerve damage (most commonly loss of feeling in the feet), kidney damage, diabetic coma,…

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