Antidiabetic plants and their active constituents.

Despite the use of a wide range of different methodologies and diagnostic criteria, epidemiological studies have shown that Type 2 (non-insulin-dependent) diabetes has a global distribution and its prevalence varies from country to country, in different ethnic groups in the same country, and between the same ethnic group undergoing internal or external migration. Rural-urban and migration studies indicate that change towards a 'Westernized' lifestyle is associated with a dramatic increase in the prevalence rates for Type 2 diabetes. Between populations, comparisons are confounded by a wide range of different ascertainment rates, survey methodologies, and diagnostic criteria for diabetes. However, low prevalence rates for Type 2 diabetes are seen in Eskimos and populations of the Far East, while the highest are seen in American Indians, urbanized Pacific Island populations, and migrant Asian Indians. Available evidence suggests that these latter groups have a genetic susceptibility to Type 2 diabetes ('diabetes genotype') and that the disease is unmasked by environmental factors. There appears to be a spectrum of interaction between genetic and environmental factors--in certain populations the genetic role may be more important than environmental, or vice versa. Epidemiological studies, apart from their value in population screenings and case-finding, have contributed to the new classification and diagnostic criteria for diabetes and our understanding of risk factors and host characteristics in the aetiology of Type 2 diabetes.

https://link.springer.com/content/pdf/10.1007/BF00282581.pdf

Type 2 (non-insulin-dependent) diabetes--an epidemiological overview.

Twelve of 129 black patients with youth-onset diabetes were identified as having an unusual clinical course, with apparent insulin dependence at the time of presentation followed by absence of dependence months to years later. This atypical form of diabetes was found in at least two generations in 9 of the 12 families of the propositi. Fourteen of the diabetic relatives, as well as the 12 propositi, were studied. Islet-cell autoantibodies were not found in any of the patients, and thyroid microsomal auto-antibodies were found in only one. The frequencies of the insulin-dependent-diabetes-associated antigens HLA-DR3 and DR4 were not increased among the propositi, and diabetes did not cosegregate with HLA haplotypes in the informative families. Insulin secretion, as measured by C-peptide responses to a liquid mixed meal (Sustacal), was intermediate between secretion in nondiabetic controls and that in patients with classic insulin-dependent diabetes. Peripheral-blood monocytes expressed increased numbers of insulin receptors as well as decreased empty-site affinities. The atypical form of diabetes in black Americans can be distinguished from classically defined insulin-dependent diabetes and may be best classified as a form of maturity-onset diabetes of youth.

Maturity-onset diabetes of youth in black Americans.

https://www.gastrojournal.org/article/S0016-5085(02)00206-8/pdf

Tropical calcific pancreatitis: strong association with SPINK1 trypsin inhibitor mutations.

An ability to visualize HCN in mitochondria in real time may permit additional insights into the critical toxicological and physiological roles this classic toxin plays in living organisms. Herein, we report a mitochondria-specific coumarin pyrrolidinium-derived fluorescence probe (MRP1) that permits the real-time ratiometric imaging of HCN in living cells. The response is specific, sensitive (detection limit is ca. 65.6 nM), rapid (within 1 s), and reversible. Probe MRP1 contains a benzyl chloride subunit designed to enhance retention within the mitochondria under conditions where the mitochondria membrane potential is eliminated. It has proved effective in visualizing different concentrations of exogenous HCN in the mitochondria of HepG2 cells, as well as the imaging of endogenous HCN in the mitochondria of PC12 cells and within neurons. Fluctuations in HCN levels arising from the intracellular generation of HCN could be readily detected.

/pdf/a-mitochondria-specific-fluorescent-probe-for-visualizing-2l72c5vown.pdf

A Mitochondria-Specific Fluorescent Probe for Visualizing Endogenous Hydrogen Cyanide Fluctuations in Neurons

Two categories of diabetes are recognized in the temperate zone—ketosis-prone diabetes requiring insulin and diabetes not requiring insulin. Another unique type of diabetes occurs in the tropics. It has two forms, both different from either form of temperate zone diabetes. Type J and pancreatic diabetes are both characterized by youth onset, antecedent malnutrition, substantial insulin requirement, and resistance to ketosis. In the tropical countries where they are found, both forms are associated with specific dietary practices, including a nutritionally marginal protein intake. The close association with low protein intake distinguishes this form of diabetes from that occurring in North America, Europe, and Oceania. The geographic distribution of malnutrition diabetes, in addition to being limited to the tropics, coincides regularly with the consumption of tapioca (cassava) or other foods that contain cyanide-yielding substances. Ingested cyanide is normally detoxified, principally, by conversion to thiocyanate. This detoxification requires sulfur, derived principally from amino acid sources. Studies in the rat indicate a remarkable ability to detoxify ingested cyanide, a reduction in urinary thiocyanate excretion when protein intake is lowered (especially during growth), production of marked hyperglycemia by either oral or parenteral cyanide, and the development of cyanosis and epidermal changes when there is prolonged exposure to cyanide. Both the association of malnutrition diabetes with food cyanogens and our laboratory observations support a role for cyanide in its pathogenesis.

D E McMillan

Papers

Dietary Cyanide and Tropical Malnutrition Diabetes