What Is Homeostasis?

Homeostasis is the body’s ability to adapt continuously — in order to maintain stable internal conditions despite external environmental shifts. At the heart of this intricate regulatory system lies the endocrine feedback loop — the foundational mechanism by which the body achieves and sustains homeostasis.

What is the Endocrine Feedback Loop?

As an endocrinologist, a clear understanding of endocrine feedback loops is paramount. These loops play a vital role in visualizing the endocrine system and, more importantly, in practicing endocrinology correctly.

What are Beta Cells?

Beta cells are a type of specialized cell found in the pancreas, an important organ in the digestive and endocrine systems of the human body. These cells are primarily known for their role in regulating blood sugar levels by producing and secreting the hormone insulin. Here is are some important facts about beta cells:

Glucagon receptor antagonist: a diabetes drug development

Glucagon and insulin work in concert to achieve and maintain proper blood glucose levels. Glucagon, released by pancreatic alpha cells, prevents hypoglycemia, while insulin released by beta cells prevents hyperglycemia. Together they preserve a tight blood glucose concentration between 70-100 mg/dL fasting and 70-140 mg/dL after meals. In type 2 diabetes, glucagon production, release, and action are malfunctioning. Overproduction of glucagon leads to over-stimulation of gluconeogenesis and glycolysis, in turn exacerbating hyperglycemia of diabetes mellitus.

It is only natural to look for ways of lowering the synthesis, secretion, or effects of glucagon. In this phase-2 clinical trial, the researchers tested the ability of a glucagon receptor antagonist in lowering A1c in 166 patients with metformin-uncontrolled type 2 diabetes over 12 weeks. The glucagon receptor antagonist RVT-1502, at the high dose 15 mg per day, lowered A1c by 1.0% without severe hypoglycemia. Slight and mild elevation of aminotransferases and blood pressure were documented respectively.

Since study results are meaningfully positive, a follow-up phase-3 randomized clinical trial would be expected.

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Interaction of ACAT with MTTP in making Lipoprotein B

Blood lipid particles, formally called lipoproteins, are essential for carrying and transporting triglycerides and cholesterol to various body tissues. Lipoproteins that contain B48 and B100 apoproteins are two decisive players. B48-Lipoprotein (Lp B48) is synthesized in the gastrointestinal tract, whereas B100-Lipoprotein (Lp B100) is made in the liver.

In this review article, the authors propose a feasible model of how Lp B48 and Lp B100 are created in the endoplasmic reticulum of enterocytes and hepatocytes. ACAT is responsible for converting free cholesterol into cholesteryl ester (CE), while MTTP is responsible for uploading CE and triglycerides into B48- or B100-Lipoproteins.

Clinician’s knowledge of Lp B48 and Lp B100 physiology is vital as both lipoproteins are – directly or indirectly – involved in all forms of dyslipidemias (Fredrickson classifications I – V)

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Prolactin Resistance

This is a nice case of prolactin resistance due to loss-of-function variant in the prolactin receptor (PRL-R) gene. A 35 year old female with hyperprolactinemia became pregnant twice, but was unable to lactate. It would take some time before the PRL-R genetic testing becomes available in clinical practice. Nonetheless, the case expands our knowledge of prolactin pathogenesis.

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The 2017 Nobel Prize in Physiology: the genetic clock

In October 2017, the nobel prize in physiology was awarded to Jeffrey C. Hall, Michael Rosbash and Michael W. Young for discovering molecular and genetic mechanisms of the biological clock.

The Nobel Prize press release is shown below, with slightly modified wording for easier and succinct reading:

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