Pancreas: Exocrine or endocrine gland?

key points: pancreas, exocrine gland, endocrine gland, pancreatic enzymes, islets of Langerhans, glucose, glucagon etc.

Do you remember studying different types of glands? Some of them were endocrine while some of them were exocrine. Before we go to Pancreas, let us first understand what are endocrine and exocrine glands?

What are endocrine glands?

Our nervous system controls and co ordinates with different organs as well as try to responds with the external environment. But human body carries several activities in various organ systems at the same time, Therefore nervous system has to maintain a balance and regulates each activity at certain time. Endocrine system brings all the co ordination and balance the activities with the help of chemical messengers called as ‘hormones’. But what does the endocrine system do? (Endo- inside and crine- separate) The system literally means secrete internally. The endocrine system consists of certain endocrine glands which perform the function of secreting hormones. They are also known as ductless glands since they release the hormones into bloodstream and not via any specialized ducts. For example, Pituitary gland- oxytocin, ADH and thyroid gland- thyroxine etc.

What are exocrine glands?

Exocrine glands require the ducts to transport the secreted substance at target site. They can not release the substance directly into bloodstream and also the substance which are produced by them shows the action at nearby areas. There are several exocrine glands such as lacrimal glands which produce tears or sweat gland for production of sweat or salivary gland for producing saliva. If you notice their function of these glands their action is restricted to certain area and shows effect around the area where they are located.

Pancreas as endocrine and exocrine glands

Liver and pancreas are the only glands in human body which act as both endocrine and exocrine glands. Let us first understand the endocrine function of pancreas.

Pancreas are located in the abdominal cavity close to duodenum and behind the stomach. They are mainly responsible for two functions are as follows:

  1. Secreting of hormones for controlling glucose (Insulin and Glucagon).
  2. Secreting digestive enzymes.

Pancreas as an endocrine gland:

Pancreas has a region called as “Islets of Langerhans” which typically consists of four cells

  1. Alpha cells
  2. Beta cells
  3. Delta cells
  4. F cells

Beta cells are responsible for producing insulin whereas alpha cells produce glucagon. Both the hormones carry the function of maintaining glucose balance inside the blood stream. The delta cells produce a hormone known as somatostatin which restrains the secretion of insulin and glucagon.

Brief mechanism of insulin and glucagon

Case I: Consider that a person had carbohydrate diet which means he is now having a lots of sugar inside the body. This is sensed by pancreas and it stimulates the beta cells to produce glucose controlling hormone called as “Insulin”.  This insulin gets released into the blood stream and bind to the glucose. This glucose is stored in the liver in the form of glycogen.

Case II: Now consider that the same person is starving and has no food to eat. In this case the pancreas stimulate alpha cells to produce “Glucagon”. Many times people get confused between glycogen and glucagon. Let’s fix this mind, glycogen is a complex form of sugar while glucagon is a hormone to break that sugar into glucose i.e. simple sugar. Hence the stored glycogen is now broken by glucagon and free glucose is released into the blood stream.

Pancreas as exocrine gland

As a duct gland it secrets digestive juices which break down the nutrients. These juices are then poured to the duodenum which is the beginning of small intestine. These enzymes travel through series of ducts and meets the pancreatic duct. The pancreatic duct meets the common bile duct and it carries bile to duodenum.

Conclusion

Pancreas secrete several enzymes which helps in the digestion. The enzymes are transported via certain ducts. Therefore Pancreas are said to have an exocrine function. Also to maintain blood sugar level it secretes hormones (insulin and glucagon) which defines its endocrine function. Hence pancreas act as both endocrine and exocrine system.

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Proteomics | SDS PAGE | Applications of Proteomics | Biology Bug

What is Proteomics?

Proteomics is the branch of molecular biology which is the large scale study of proteomes. But what is proteome? A proteome is set of proteins produced in an organism, a system or biological context. Proteome can be studied in specific organism (human, rat) or can be studied in specific organ (liver, pancreas). The proteome is not constant because it differs from cell to cell and changes over a period of time.

Importance of proteome analysis

Proteins are not only the important macromolecules in our body but also the most common effectors of disease pathogenesis and determinants of treatment response. But analysis of proteins is technically challenging and hence we face troubles to develop effective therapeutics. However analysis of DNA and RNA have some role in the prediction of protein function but these results do not always correlate with protein functions. Proteomics help us to overcome these challenges and also in the prediction of protein functions at different levels like post translational modification, domains, motif etc. Despite the inherent limitations of proteomic methodologies, as many as 115 protein based assays have been approved for use by regulatory agencies and commercialize with the great success.

SDS-PAGE or Gel elctrophoresis

Gel based proteomic is the most popular and versatile method of global protein separation and quantification. This is mature approach to screen the protein expression at the large scale. Based on two biochemical characteristics of proteins, two dimensional electrophoresis combines isoelectric focusing which separates proteins according to their isoelectric point and SDS PAGE which separates them further according to their molecular mass. The next typical steps of flow of gel based proteomics are spots visualization and evaluation, expression analysis and finally the protein identification by mass spectrometry. For the study of differentially expressed proteins, two dimensional electrophoresis allows simultaneously to detect, quantify and compare up to thousand protein spots isoform including post translational modifications in the same gel and in a wide range of biological systems.

First dimension

Proteins are amphoteric molecules i.e. they carry both positive and negative charge; hence the net charge on proteins is zero depending upon their amino acid composition. The isoelectric point of protein is the specific pH at which the net charge of protein is zero. Proteins are positively charged at pH values below their isoelectric point and are negatively charged at pH values above their isoelectric point. IEF is an electrophoretic separation based on this specific characteristics of proteins.

Basically the first dimension of two dimensional electrophoresis is achieved with a strip. It is a dry gel that is formed by the polymerization of acrylamide monomers, linked by bis-acrylamide with molecules of covalently linked immobilin, immobilins are chemical components that are derived from  acrylamide and have additional ionizable non amphoteric functions. Immobilins of various pKa can create am immobilized pH gradient inside the gel.

The strip acrylamide gels are dried and cast on a plastic backing. They are rehydrated in a solution containing a pI- corresponding cocktail of carrier ampholytes and with the correct amount of the proteins in the solubilization buffer. The carrier ampholytes are amphoteric molecules with high buffering capacity near their pI.

When an electric field is applied, the negatively charged molecules (proteins and ampholytes) move towards the anode (red electrode) and the positively charged molecules move towards cathode (black electrode). When the proteins are aligned according to their isoelectric point, the global net charge is zero and the protein is unable to move and is then focused. Focusing is achieved with a dedicated apparatus that is able to deliver up to 8000-10000 V, but with a limitation in current intensity to reduce heat.

The equilibration step is critical for 2DE. In this step the strips are with sodium dodecyl sulfate (SDS), an anionic detergent that can denature proteins and form a negatively charged protein complex. The amount of SDS bound to a protein is directly proportional to the mass of protein. Thus, protein that are completely covered by negative charges are separated on the basis of molecular mass.

Second dimension

The SDS denatured and reduced proteins are separated according to an apparent molecular weight, in comparison with a molecular weight maker. Equilibrated strips are embedded with 1% low melting point agarose in TRIS/Glycine/ SDS running buffer and 0.01% bromophenol blue on the top of second dimension gel. When the bromophenol blue migration front reaches the bottom of the gel, the second dimension is finished and the acrylamide gel can be removed from the glass plates.

Application of Proteomics

Mining

Expression profiling

Network mapping

Protein modification

Mining

It is a process of analysing and identifying all the protein samples. Mining is one of the ultimate excercise in proteomics where one simply resolves proteins to the greatest extent possible. It uses MS with associated database and software tools to identify what exactly is found. The several approaches of mining offer the ability to confirm

Expression profiling

Protein Expression profiling is identification of proteins at different level of stages of organsims or cells eg. Development or disease state. Also to analyze the expression due to some genetic, chemical or physical stimulus eg drug. Expression profiling is actually a specialzed form of mining. It is used especially in the cases where two different stages are compared to see which proteins are expressing differently. This technique is used to detect the potential targets for drug therapy and disease.

Protein network mapping

It is an approach to determine how exactly proteins react with each other in a living system. Protein carry out their function in close association with other proteins. They involve in signal transduction, complex biosynthetic and degradation pathways. Most of the protein protein interaction has been studied in vitro. Then why network mapping is important? Proteomic approaches offer the opportunity to characterize more complex network through creative pairing of affinity capture techniques with analytical proteomics methods. They used to identify the components of multiprotein complexes. Multiple complexes are involved in point to point signal transduction pathways in cells. This technique helps to understand all the components in single pathway.

Protein modifications

Another application of proteomics analysis is to identify how and where the proteins are modified. There are many common post translational modifications which can govern the structure, function and turnover of protein. Also many chemicals, environmental factors or drugs can influence the modification of protein. These modified proteins can be detected with antibiodies but the precise sequence sites of specific modification are not known. Proteomics approaches offer the best  means of establishing both the nature and the sequence of posttranslational modifications. These approaches will provide of chemical modifications in domain.

External links

  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2873371/
  • https://academic.oup.com/hmg/article/25/R2/R182/2198199
  • https://www.ebi.ac.uk/training/online/course/proteomics-introduction-ebi-resources/what-proteomics

Types and causes of moles- Biology Bug

What are moles?

Moles are the growth on the skin which are brown, black or red colored lesions which can appear alone or exist in groups. They can appear anywhere on your body including the eyes, nose, hands, legs, chest, back or even the genitals. The medical term for the moles is melanocytic nevus (visible chronic lesions on skin). Some people describe them as imperfection on the body while most of the beauty experts consider them as beauty mark. Most of the times moles appear in early childhood and during first 25 years. But have you ever thought what the factors which cause mole are? Let’s discuss some of them.

What causes mole?

  • Exposure to sun
  • Genetic factors
  • Hormonal imbalance

Exposure to sun

Every individual gets a distinct skin color because of different melanin levels. Melanin is a pigment which is produced by specialized skin cells called as melanocytes. These melanocytes produces more melanin when exposed to sun in order to protect the skin from harmful radiation. This is one of the reason why we get tan when exposed to the sun. Moles are concentrated clumps of melanocytes, which is why they look darker. A normal individual can have 15-30 moles. However the people with more number of moles have higher risk of melanoma. Melanoma is a type of cancer that develops from melanocytes. But most of the moles are non-carcinogenic in nature.

Role of genetics

The role of genetics is not well understood for mole development. However the study for melanoma has been widely published and hence we can relate it to development of benign moles. DNA present in the skin cells contains several genes. There can be mutation, hereditary factors or exposure to harmful radiation can result into variation of certain genes which includes FGFR3, PIK3CA, HRAS, and BRAF. Variation in these genes can lead to benign moles. For example, mutation in BRAF gene leads to production of an altered protein that causes melanocytes to aggregate into moles. 

Hormonal imbalance

Hormones can be imbalanced because of several reasons including pregnancy, menopause, puberty or medications. During pregnancy the level of progesterone and estrogen vary each month. Also there is small variation in amount of MSH i.e. melanocyte stimulating hormone which is produced by pituitary gland. MSH hormones stimulate the melanin production in melanocytes. Hence you can see dark or tan patches on the skin in case of pregnant ladies. It frequently occurs during the menopause since the hormonal level is fluctuating continuously and results into increase in either the size of mole or number of moles.

Types of moles

There are basically three types of moles that are symmetrical, irregular and regular. But in medicine it is divided into several types according to their location, shape and time of appearance.

Common moles

It is about 5mm large with distincy edges and dome like surface with brown pigmentation. They are found on the skin when exposed to the sun.

Atypical

This type of mole shows irregular symptoms. They have blurry borders and can vary in color. They are comparatively larger than the common moles. Also they can be flat or raised lesions. If a person is having too many atypical moles then the risk of skin cannot be neglected. The person should go for regular examination.

Congenital moles

They are also known as congenital nevi. They appear at the time of birth or within first year of baby’s life. These moles can be caused by melanocyte cells in middle layer of skin, outer layer of skin or both. They can be referred as birthmarks.

Acquired moles

Acquired moles are moles that appear during childhood and adulthood. Most of these moles are benign and pose no risk, although sometimes they can turn into cancerous moles with age. This type of mole is the most common, and repeated sun exposure usually causes it. These moles appear during early childhood or sometimes in adulthood. This type of mole generally do not pose any risk in future. They are one of the commonly seen moles.

Junctional melanocytic moles

They occur due to accumulation of melanocytes where the dermis and epidermis meet. They are slightly raised with regular borders and dark pigmentation (range from tan to dark brown). As the age increases these moles can migrate down to deeper layers of skin.

Intradermal moles

They are skin colored moles and their pigmentation is not as dark as junctional ones because they are located in the middle layer of your skin. They usually develop during late childhood or throughout the adulthood.

 Now remembering all the types of moles with their unique qualities can be little difficult. Hence doctors have introduced ABCDE method.

A: Asymmetrical

B: Irregular border

C: Multiple color

D: Bigger diameter

E:  Evolving, new or changing

External Links:

  • https://www.webmd.com/skin-problems-and-treatments/guide/moles-freckles-skin-tags
  • https://www.healthline.com/health/new-mole#types
  • https://www.medicinenet.com/moles/article.htm#what_are_moles
  • https://ghr.nlm.nih.gov/primer/traits/moles
  • https://www.skinvision.com/articles/types-of-skin-moles-and-how-to-know-if-they-re-safe

Thanks for reading. Tell me which type of mole you’ve seen? Comment down below.